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APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 1
LEUKEMIA COMMITTEE
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 2
CONTENTS
Initial Registrations to Therapeutic Studies . . . . . . . . . . . . . . . . . . . . . 3
Patient Registration by Study and Arm . . . . . . . . . . . . . . . . . . . . . . . 4
S9007 Biologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
S9910 Biologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
S0325 Phase IIb Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
S0521 Phase III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
S0535 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
S0703 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
S0805 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
S0910 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
S0919 Phase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
C10403 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
C10404 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
C10603 Phase III SWOG Endorsed CTSU Study . . . . . . . . . . . . . . . . 51
C10701 Phase II SWOG Endorsed CTSU Study . . . . . . . . . . . . . . . . . 53
E1905 Phase II Intergroup . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
E1908 Phase II SWOG Endorsed CTSU Study . . . . . . . . . . . . . . . . . . 57
E2905 Phase III SWOG Endorsed CTSU Study . . . . . . . . . . . . . . . . . 59
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 3
Initial Registrations to Therapeutic Studies
by 12 Month Intervals
LEUKEMIA COMMITTEE
0
50
100
150
200
250
300
350
400
450
Time of registration
JAN 2005DEC 2005
160
16
70
161
JAN 2006DEC 2006
99
14
50
125
JAN 2007DEC 2007
140
9
50
142
JAN 2008DEC 2008
164
8
49
199
JAN 2009DEC 2009
125
12
55
131
JAN 2010DEC 2010
88
825
28
MEMBER AFFILIATE CCOP NON-SWOG
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 4
Patient Registration by Study and Arm
LEUKEMIA COMMITTEE
July-Dec
2010
Jan-June
2010
July-Dec
2009
All
Patients
S9007 Cytogenetic Studies in Leukemia Patients
Cytogenetics Samples 2 33 70 3,315 S9910 Leukemia Central Lab/Tissue Repository
Specimen Submission 1 33 71 1,265 S0106 AML, Mylotarg/Ara-C/Daunomycin
ARA-C + Daunomycin + Mylotarg 0 0 13 317
ARA-C + Daunomycin 0 0 11 320
0 0 24 637 S0333 Non-L3 ALL, Double Induction DNR + VCR + Pred + PEG-L-Asp 0 0 3 79 S0521 APL, Low/Int Risk, Maint vs Obs
ATRA + ARA-C + Daunorubicin 0 23 31 105 S0535 APL, High Risk, ATRA/arsenic/G.O.
ATRA + G.O. + Arsenic 0 17 9 34 S0605 AML, del5q, Age 60+, Revlimid
Revlimid 0 2 6 41 S0703 AML, age 60+, Azacitidine G.O.
Hydroxyurea/Azacitidine/G.O. 0 38 37 90 S0805 Ph+ ALL, Dasatinib/CVAD +/- BMT
Induction/Consolidation 1 0 0 1 S0910 Rel Ph-,B-ALL, Epratuzumab+Cy+Clo
ARA-C+Clofarabine+Epratruzumab 3 0 0 3 S0919 Rel AML: Pravastatin+Ida+Ara-C
Pravastatin+Idarubicin+Ara-C 5 4 1 10 C10403 Adolescent/Young Adult ALL *
Sequential Chemotherapy 11 14 5 35 C10404 CLL, Flu/Rituxan combinations *
Flu/Rituximab 1 1 1 3 Flu/Rituximab/Lenalidomide 2 0 1 3
Flu/Cy/Rituximab 2 1 1 4
5 2 3 10 C10501 CLL, Early Intervention vs Obs * Total Registrations 0 0 2 8 C10603 AML PKC 412, blinded, FLT3 *
Total Registrations 12 5 1 20 E1905 MDS/CMMoL/AML-TLD, Aza +/- MS-275 *
Azacitidine 0 0 0 8
Azacitidine + MS-275 0 2 0 14
0 2 0 22 E2905 MDS, Len vs Len + Epo * Total Registrations 2 3 7 12
* For non-SWOG coordinated studies only SWOG registrations are shown.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 5
S9007/BIOLOGIC
S9007 Biologic
Coordinating Group: SWOG
Cytogenetic Studies in Leukemia Patients
Participants: SWOG, CTSU
Study Coordinator: D Roulston
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 7/15/1991
Objectives To estimate the frequencies and prognostic signi-
ficance of cytogenetic abnormalities in marrow or
blood cells of leukemia patients prior to treatment
on SWOG protocols and at various times in the
course of their treatment.
To estimate correlations between the presence of
cytogenetic features and of clinical, pathophysio-
logical, cellular, or molecular characteristics in these patients.
To provide quality control for all SWOG cytoge-
netic data.
Patient Population Patients must be registered to any SWOG leuke-
mia protocol approved after January 1, 1990, in-
cluding ECOG patients registered to S9300.
Summary Statement As of December 31, 2010, a total of 3,315 pa-
tients were registered on this study.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 6
S9007/BIOLOGIC
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg Institutions Total
Reg
Wichita CCOP
201 Oregon Hlth Sci Univ
28Loyola University 161 LSU-New Orleans CCOP 27Puget Sound 128 Southeast CCC CCOP 27Michigan, U of 124 South Alabama CCOP 25City of Hope Med Ctr 119 Stanford University/City of Hope Med Ctr 25LSU-Shreveport 107 Cincinnati MC, U of 24Columbus CCOP 97 Scott & White/TX A&M 24Wayne State Univ 93 Mississippi, Univ of 23Cleveland Clinic OH 88 Virginia Mason CCOP 22Utah, U of 79 Oklahoma, Univ of 21Ohio State U 76 Breslin Cancer Ctr/Henry Ford Hosp 20Rochester, Univ of 72 Kaiser, Sacramento/Davis, U of CA 19Kansas City CCOP 66 BAMC/WHMC 18Davis, U of CA 61 H Lee Moffitt CC 17Henry Ford Hosp 58 Riverside Methodist/Ohio State U 17St Louis CCOP 55 Sutter Hlth Western/Davis, U of CA 17Dayton CCOP 54 Akron Gen Med Ctr/Cleveland Clinic OH 16St Louis University 52 CALGB 14Stanford University 52 Carilion Medical Ctr/Temple University 13Upstate Carolina 49 Scott & White CCOP 13Central IL CCOP 48 Temple University 13San Antonio, U of TX 48 Allegheny CCOP 12MUSC, Hollings CC 45 Michael Reese Hosp/Oklahoma, Univ of 12Arkansas, U of 44 Michigan CRC CCOP 12Montana CCOP 42 Northwest CCOP 12Arizona, U of 39 Tulane Univ/San Antonio, U of TX 11Atlanta Reg CCOP 39 Aultman Hospital/Ohio State U 10Stormont-Vail Health/Kansas, U of 38 Hawaii MBCCOP, U of 10So Calif, U of 36 LSU-Shreveport CCOP 10Boston Univ Med Ctr 33 Tulane University 10ECOG 33 NCCTG 9Grand Rapids CCOP 32 Salem Hospital/Oregon Hlth Sci Univ 9Providence Hosp 32 SW Cancer & Res Ctr/San Antonio, U of TX 9New Mexico, U of 30 Thompson Ca Surv Ctr/San Antonio, U of TX 9Colorado, U of 29 Hawaii, U of 8New Mexico MBCCOP 29 Santa Rosa Mem Hosp/Davis, U of CA 8
Columbia River CCOP 28 All Other Institutions 296
Kentucky, U of 28 Total (196 Institutions) 3,315
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 7
S9910/BIOLOGIC
S9910 Biologic
Coordinating Group: SWOG
Leukemia Centralized Reference Laboratories and Tissue Repositories,
Ancillary
Participants: SWOG, CTSU
Study Coordinators: C Willman, J Radich
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 4/15/1999
Objectives To develop and apply laboratory assays for the
rapid and precise diagnosis of leukemia patients
and identify biologic, genetic, and molecular pa-
rameters that distinguish different subtypes of
human leukemia with differing responses to ther-
apy.
To develop "risk-adapted" therapeutic approaches
in which biologic, genetic, and molecular para-meters are used to target individual patients to tai-
lored therapeutic regimens, or, to randomize and
stratify patients to different treatment arms of a
therapeutic trial.
To develop new automated and standardized la-
boratory methods for the detection and monitor-
ing of therapeutic responsiveness and minimal re-
sidual disease in leukemia patients and develop
new clinical approaches to employ such data in therapeutic decision making and clinical trial de-
sign.
To maintain and expand tissue repositories of
highly characterized leukemia samples from un-
iformly treated SWOG patients to promote inter-
group and external fundamental scientific colla-
borations and to perform continued critical pros-
pective and retrospective correlative biologic stu-
dies.
To utilize scientific information generated from
intergroup and collaborative studies to assist the Leukemia Committee in the development of new
and more effective treatment regimens.
Patient Population Patients must be registered on a SWOG treatment
study for lymphoid leukemia (ALL or CLL),
myeloid leukemia (AML or CML) or myelodys-
plasia on or after the date of activation of this
study.
Summary Statement As of December 31, 2010, 1,265 patients were
registered to this study.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 8
S9910/BIOLOGIC
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg Institutions Total
Reg
Michigan, U of
108 Providence Hosp
19 Wichita CCOP 95 Kansas City CCOP 18 Loyola University 93 H Lee Moffitt CC 17 Rochester, Univ of 72 Dayton CCOP 15 Puget Sound 55 Oregon Hlth Sci Univ 15 Stanford University 50 Kentucky, U of 14 Columbus CCOP 48 St Louis CCOP 14 MUSC, Hollings CC 45 CALGB 13 Utah, U of 43 Davis, U of CA 13 Cleveland Clinic OH 39 Arizona, U of 12 Wayne State Univ 38 San Antonio, U of TX 12 City of Hope Med Ctr 32 LSU-Shreveport CCOP 10 New Mexico MBCCOP 32 Stanford University/City of Hope Med Ctr 10 LSU-Shreveport 28 Arkansas, U of 9 Southeast CCC CCOP 25 Atlanta Reg CCOP 9 Grand Rapids CCOP 22 Henry Ford Hosp 9 Upstate Carolina 22 NCCTG 9 Montana CCOP 21 So Calif, U of 9 Central IL CCOP 20 Sutter Hlth Western/Davis, U of CA 8 ECOG 20 All Other Institutions 102 Stormont-Vail Health/Kansas, U of 20 Total (78 Institutions) 1,265
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 9
S0325/IIB
S0325 Phase IIb Intergroup
Coordinating Group: SWOG
A Phase IIb Study of Molecular Responses to Imatinib at Standard or
Increased Doses, or Dasatinib (BMS-354825)(NSC-732517) for Previously
Untreated Patients with Chronic Myelogenous Leukemia (CML) in Chronic
Phase
Intergroup Participants: SWOG, CALGB (10303), ECOG, NCIC CTG (CM.1)
Study Coordinators: B Druker, M Slovak, J Radich, P Emanuel (ECOG),
M Wadleigh (CALGB), J Lipton (NCIC CTG)
Statisticians: K Kopecky, H Gundacker
Data Coordinator: T Maher
Date Activated: 8/15/2004
Date Closed: 2/28/2009
Schema
R
A
N
D
O
M I
Z
E
Chronic phase
CML within 6
months of diagnosis
Imatinib 400 mg/day
Dasatinib 100 mg/day*
E
V
A
L
U A
T
E
Level of molecular
response at 1 year Imatinib 800 mg/day*
* Accrual to the dasatinib arm began on November 29, 2006.
Accrual to the imatinib 800 mg/day arm was closed on February 1, 2007.
Objectives To compare the molecular response, as measured
by the decrease in BCR-ABL transcripts after 12
months of treatment, in patients with previously
untreated CML in chronic phase who are treated with either dasatinib 100 mg/day or imatinib
(STI-571, Gleevec®) 400 mg/day.
To test whether increasing the dose of imatinib
(STI-571, Gleevec®) from 400 mg/day to 800
mg/day increases the rate of molecular response,
as measured by the decrease in BCR-ABL tran-
scripts after 12 months of treatment, in patients
with previously untreated CML in chronic phase.
To estimate rates of cytogenetic and hematologic
responses to imatinib 400 mg/day, imatinib 800
mg/day, and dasatinib 100 mg/day.
To evaluate in a preliminary manner the prognos-
tic effects of der(9) and der(22) chromosomal de-
letions for response in CML patients treated with
imatinib and dasatinib.
To investigate in a preliminary manner changes
in gene expression at relapse or progression com-
pared to pre-treatment.
To estimate the frequency and severity of toxici-ties of the three treatment regimens.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 10
S0325/IIB
To evaluate, in a preliminary manner, the overall
survival and relapse-free survival of patients
treated with these regimens.
Patient Population Patients must have a diagnosis of CML in chronic
phase based on bone marrow aspiration and biop-
sy and peripheral blood counts obtained within 28
days before registration. Patients must be regis-
tered on this study within 180 days after the date
of first being diagnosed with CML, based on a
cytogenetic or molecular analysis demonstrating
the presence of the Philadelphia chromosome or
variants of the (9;22) translocation or testing
positive for BCR-ABL by RT-PCR. Patients may
have secondary chromosomal abnormalities in
addition to the Philadelphia chromosome and re-main eligible.
Patients must not have received prior treatment
for CML with the exception of hydroxyurea
and/or anagrelide. Patients must not have re-
ceived any prior chemotherapy regimen for peri-
pheral blood stem cell mobilization. Patients must
not have undergone major surgery within 28 days
before registration, and must have fully recovered
from any other prior major surgery.
Patients must have reached their 18th birthdays,
have a Zubrod performance status of 0, 1, or 2,
and have adequate hepatic function. Patients must
not have the following cardiac symptoms prior to
entry on study: uncontrolled angina, congestive
heart failure or MI within six months of study en-
try, diagnosed or suspected congenital long QT
syndrome, any history of clinically significant
ventricular arrhythmias (such as ventricular ta-
chycardia, ventricular fibrillation, or Torsades de pointes), prolonged QTc interval on pre-entry
electrocardiogram (> 45 msec), or uncontrolled
hypertension. Patients must not have a history of
significant bleeding disorder unrelated to cancer,
including congenital bleeding disorders (e.g., von
Willebrand's disease) and acquired bleeding dis-
order within one year (e.g., acquired anti-factor
VII antibodies).
Stratification/Descriptive Factors Patient randomization will be stratified by Has-
ford risk category: low vs intermediate vs high.
Accrual Goals The total accrual goal for this study is 400 eligi-
ble patients with 240 randomized between dasati-
nib and low dose imatinib. One interim analysis
will be conducted during the course of this study,
when the 12-month molecular response can be
evaluated for 120 eligible post-amendment pa-
tients (approximately 60 patients for each of the imatinib 400 mg/day and dasatinib arms).
Summary Statement Effective November 29, 2006, this study was
modified to add a third study arm of dasatinib
100 mg/day. The imatinib 800 mg/day arm was
closed to accrual on February 1, 2007. Accrual to
the two remaining arms was closed on February 28, 2009 because the accrual goal was met.
A total of 403 patients were registered to this
study. The following summary is presented in
two parts corresponding to the first two study ob-
jectives. The first part is based on the 153 patients
who were concurrently randomized between the
two imatinib arms, and the second part on the 253
patients who were concurrently randomized be-
tween imatinib 400 mg/day and dasatinib. Note
that the three patients who were registered when all three arms were open are included in both
parts.
1. Imatinib 400 mg/day (standard dose) versus
Imatinib 800 mg/day (high dose):
Seven of the 153 patients on these arms did not
have CML in chronic phase and are ineligible and
excluded from the analysis. One patient who did not receive protocol therapy due to lack of insur-
ance coverage is also excluded from the analysis.
Five major protocol deviations were reported
among the 145 analyzable patients. Two patients
had a prolonged discontinuation of protocol ther-
apy and two others continued to receive protocol
therapy after treatment failure. These four pa-
tients are included in the analysis. A fifth patient
randomized to the high dose arm received the
standard dose regimen. This patient is excluded from the toxicity analysis but is included in all
other analyses.
Six patients were removed from each regimen
due to various toxicities. All 34 patients who
were removed from protocol therapy for reasons
other than progression or death have been eva-
luated for hematologic response, and 28 (82%)
achieved complete hematologic responses.
No fatal toxicities have been reported on either
imatinib arm. Various Grade 4 toxicities, most
commonly hematologic, were reported for nine
(13%) of 72 patients evaluated for toxicities on
the standard dose regimen, and for ten (14%) of
72 patients on the high dose arm. Grade 3 fatigue
was reported for 11 (15%) patients in the high
dose arm, but none in the standard dose arm.
Sixty-three (88%) of the 72 patients evaluated for hematologic response in the standard dose arm
achieved a complete hematologic remission (CR)
or unconfirmed hematologic CR (95% confidence
interval, 78% to 94%). On the high dose arm, 66
(90%) of the 73 patients evaluated for hematolog-
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 11
S0325/IIB
ic response achieved a confirmed or unconfirmed
hematologic CR (95% confidence interval, 81%
to 96%).
Five (10%) of 49 patients with 12-month follow-up specimens assayed by RT-PCR achieved mo-
lecular response (4-log reduction of BCR-
ABL/BCR ratio) in the standard dose arm (95%
confidence interval 3% to 22%), compared to 14
(25%) of 55 on the high dose arm (95% confi-
dence interval 15% to 39%, p=0.073).
Five patients on the standard dose arm have died
for a two-year survival rate of 89%. Two patients
on the high dose arm have died for a two-year
survival rate of 95%. There is no statistically sig-nificant difference in overall survival between the
two doses of imatinib (log rank p-value=0.29). Of
the 63 patients who achieved a hematologic re-
mission with the standard dose, six patients re-
lapsed and three died without a report of relapse
for a two-year relapse-free survival rate of 83%.
Of the 66 patients who achieved a hematologic
remission with the high dose, two patients re-
lapsed and a third died without a report of relapse
for a two-year relapse-free survival rate of 97%.
There is no statistically significant difference in relapse-free survival between the two doses of
imatinib (log rank p-value=0.074).
2. Imatinib 400 mg/day versus Dasatinib:
Two hundred fifty-three patients were rando-
mized between these arms. Five were ineligible
and excluded from this analysis: two with Ph-
negative disease, two who did not have CML in
chronic phase, and one with prolonged QTc in-terval. Two patients on the imatinib arm are not
evaluable and excluded from the analysis: one did
not receive protocol therapy due to lack of insur-
ance coverage and the other withdrew consent af-
ter four days of protocol treatment.
Three major protocol deviations were reported,
all for patients randomized to dasatinib. Two pa-
tients received only half of the protocol dose: one
due to patient error and one due to non-compliance. A third patient randomized to the da-
satinib arm received the imatinib standard dose
regimen and is also a major protocol deviation.
This patient is excluded from the toxicity analysis
but is included in all other analyses.
Fifteen patients were removed from the imatinib
arm and 19 from the dasatinib arm due to various
toxicities. All 79 patients who were removed
from protocol therapy for reasons other than pro-
gression or death have been evaluated for hema-
tologic response, and 62 (78%) achieved com-
plete hematologic responses.
No fatal toxicities have been reported for either the imatinib or dasatinib arm. Of the 123 imatinib
patients evaluated for toxicities, Grade 4 toxici-
ties were reported for two patients (2%): one with
thrombocytopenia and one with neutropenia and
thrombocytopenia. Grade 4 toxicities were re-
ported for 17 (14%) of 122 patients evaluated for
dasatinib toxicity, most commonly hematologic.
Grade 4 non-hematologic toxicities were reported
for seven patients on the dasatinib arm: febrile
neutropenia in two patients, and elevated LDH
(coded as Metabolic/Lab-other), cardiac ische-
mia/infarction, conduction abnormality asystole, pericardial effusion, and sensory neuropathy in
one patient each.
One hundred twelve (91%) of the 123 patients
evaluated for hematologic response in the imati-
nib arm achieved a complete hematologic remis-
sion (CR) or unconfirmed hematologic CR (95%
confidence interval, 85% to 95%). On the dasati-
nib arm, 107 (87%) of the 123 patients evaluated
for hematologic response achieved a confirmed or unconfirmed hematologic CR (95% confidence
interval, 80% to 92%).
Among patients with follow-up specimens as-
sayed by RT-PCR, the rate of molecular response
(4-log reduction of BCR-ABL/BCR ratio) at 12
months was 18/90 (20%, 95% confidence interval
12% to 30%) on the imatinib arm and 27/99
(27%, 95% confidence interval 19% to 37%) on
the dasatinib arm, which is not a significant dif-
ference (p=0.31).
Four patients on the imatinib arm have died for a
two-year survival rate of 98%. Three patients on
the dasatinib arm have died for a two-year sur-
vival rate of 97%. There is no statistically signifi-
cant difference in overall survival between the
imatinib and dasatinib arms (log rank p-
value=0.55). Of the 112 patients who achieved a
hematologic remission on the imatinib arm, five
patients relapsed and two died without a report of relapse for a two-year relapse-free survival rate of
95%. Of the 107 patients who achieved a hemato-
logic remission on the dasatinib arm, three pa-
tients relapsed and another died without a report
of relapse for a two-year relapse-free survival rate
of 96%. There is no statistically significant dif-
ference in relapse-free survival between these two
arms (log rank p-value=0.29).
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 12
S0325/IIB
Initial Registrations By 3 Month Intervals
0
10
20
30
40
50
Time of Registration
OCTDEC2004
3
3
JANMAR2005
21
APRJUN2005
4
4
JULSEP2005
8
13
OCTDEC2005
10
5
JANMAR2006
9
13
APRJUN2006
7
12
JULSEP2006
15
11
OCTDEC2006
15
14
JANMAR2007
6
5
2
APRJUN2007
18
11
JULSEP2007
13
11
OCTDEC2007
12
18
JANMAR2008
21
27
APRJUN2008
15
15
JULSEP2008
15
14
OCTDEC2008
16
16
JANMAR2009
10
9
Dasatinib Imatinib 400 mg/day Imatinib 800 mg/day
Registration by Institution
Institutions
Total
Reg
Institutions
Total
Reg
ECOG
108 Kansas City CCOP
4
NCIC-CTG 87 Rochester, Univ of 4CALGB 74 Loyola University 3Columbus CCOP 16 St Louis CCOP 3Michigan, U of 13 Puget Sound 2Wichita CCOP 13 St Louis University 2Utah, U of 10 Upstate Carolina 2City of Hope Med Ctr 8 Dayton CCOP 1Montana CCOP 8 Mansfield Gen Hosp/Cleveland Clinic OH 1Southeast CCC CCOP 8 MD Anderson, Florida/Arkansas, U of 1Central IL CCOP 7 Michigan CRC CCOP 1Oregon Hlth Sci Univ 7 San Antonio, U of TX 1So Calif, U of 7 Singing River Hosp/Mississippi, Univ of 1
Providence Hosp 5 St Joseph Hospital/Puget Sound 1
Stormont-Vail Health/Kansas, U of 5 Total (29 Institutions) 403
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 13
S0325/IIB
Registration, Eligibility, and Evaluability
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
TOTAL
Imatinib
400 mg/day
Imatinib
800 mg/day
NUMBER REGISTERED
153 75 78
INELIGIBLE 7 2 5 ELIGIBLE 146 73 73 Not Analyzable 1 1 0 RESPONSE ASSESSMENT Determinable 136 67 69 Not Determinable 9 5 4 ADVERSE EVENT ASSESSMENT Evaluable 144 72 72 Not Evaluable 1 0 1
Patient Characteristics
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
Imatinib 400 mg/day Imatinib 800 mg/day
(n=72) (n=73)
AGE Median
50.8
52.1
Minimum 23.9 20.0 Maximum 80.4 82.4 SEX Males
46
64% 47
64%
Females 26 36% 26 36% HISPANIC Yes
0
0% 1
1%
No 47 65% 48 66% Unknown 25 35% 24 33% RACE White
44
61% 55
75%
Black 5 7% 3 4% Asian 1 1% 2 3% Unknown 22 31% 13 18% HASFORD RISK CATEGORY Low
15
21% 15
21%
Intermediate 22 31% 22 30% High 35 49% 36 49%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 14
S0325/IIB
Treatment Summary
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
TOTAL
Imatinib
400 mg/day
Imatinib
800 mg/day
NUMBER ON PROTOCOL TREATMENT
14 10 4
NUMBER OFF PROTOCOL TREATMENT 131 62 69 REASON OFF TREATMENT Treatment completed as planned 89 37 52 Adverse Events or side effects 12 6 6 Refusal unrelated to adverse events 12 7 5 Progression/relapse 6 4 2 Death 2 1 1 Other - not protocol specified 10 7 3 Reason under review 0 0 0MAJOR PROTOCOL DEVIATIONS 5 2 3
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 15
S0325/IIB
Number of Patients with a Given Type and Grade of Adverse Event
Imatinib 400 mg/day versus Imatinib 800 mg/day
Adverse Events Unlikely or Not Related to Treatment Excluded
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Data as of February 9, 2011
Imatinib
400 mg/day
Imatinib
800 mg/day
(n=72) (n=72)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ≤ 2 3 4 5
ALT
71 1 0 0 69 2 1 0
AST 71 1 0 0 71 0 1 0Bilirubin 71 1 0 0 72 0 0 0Blurred vision 71 1 0 0 71 1 0 0CPK 69 2 1 0 72 0 0 0Diarrhea 71 1 0 0 66 6 0 0Distension 72 0 0 0 71 1 0 0Dizziness 71 1 0 0 72 0 0 0Dyspnea 72 0 0 0 70 2 0 0Edema-head and neck 70 1 1 0 72 0 0 0Edema-limb 72 0 0 0 70 2 0 0Edema-trunk/genital 72 0 0 0 71 1 0 0Edema-viscera 71 1 0 0 72 0 0 0Fatigue 72 0 0 0 61 11 0 0Febrile neutropenia 71 1 0 0 71 1 0 0GGT 72 0 0 0 71 1 0 0GI Inf, 0-2 ANC: colon 72 0 0 0 71 1 0 0GI Pain: abdomen 71 1 0 0 68 4 0 0GU Inf, 0-2 ANC: UTI 71 0 1 0 72 0 0 0Hemoglobin 67 4 1 0 64 7 1 0Hepatobiliary-other 72 0 0 0 71 1 0 0Hypoxia 72 0 0 0 71 1 0 0Leukocytes 71 1 0 0 70 2 0 0Lung Inf, 0-2 ANC: lung 72 0 0 0 71 1 0 0Lung Pain: chest/thorax 72 0 0 0 71 1 0 0Lymphopenia 71 0 1 0 71 1 0 0Mood alteration: depression 71 0 1 0 72 0 0 0Muscle weakness: whole body 72 0 0 0 71 1 0 0Musculo. Pain: back 72 0 0 0 71 1 0 0Musculo. Pain: bone 71 0 1 0 69 3 0 0Musculo. Pain: joint 72 0 0 0 71 1 0 0Musculo. Pain: limb 72 0 0 0 71 1 0 0Musculo. Pain: muscle 71 1 0 0 69 3 0 0Nausea 70 2 0 0 70 2 0 0Neuro Pain: head/headache 71 1 0 0 71 1 0 0Neutrophils 64 5 3 0 60 8 4 0Platelets 66 5 1 0 58 8 6 0Pruritus 72 0 0 0 71 1 0 0Rash 71 1 0 0 68 3 1 0Restrictive cardiomyopathy 72 0 0 0 71 1 0 0Vomiting 71 1 0 0 72 0 0 0Weight gain 72 0 0 0 71 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Number
50 13 9 0 30 32 10 0
Hematologic Response
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
Imatinib
400 mg/day
Imatinib
800 mg/day
Complete Response
59 82% 62 85%
Unconfirmed Complete Response 4 6% 4 5%Stable/No Response 4 6% 2 3%Increasing Disease 0 0% 1 1%Assessment Inadequate 5 7% 4 5% Total
72 100% 73 100%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 16
S0325/IIB
Overall Survival by Treatment Arm
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
0%
20%
40%
60%
80%
100%
0 24 48 72
Months since Complete Remission
Imatinib 800 mg/day
Imatinib 400 mg/day
At Risk
73
72
Deaths
2
5
2-Year
Estimate
95%
89%
Relapse-Free Survival by Treatment Arm
Imatinib 400 mg/day versus Imatinib 800 mg/day
Data as of February 9, 2011
0%
20%
40%
60%
80%
100%
0 24 48 72
Months since Complete Remission
Imatinib 800 mg/day
Imatinib 400 mg/day
At Risk
66
63
Failed
3
9
2-Year
Estimate
97%
83%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 17
S0325/IIB
Registration, Eligibility, and Evaluability
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
TOTAL
Imatinib
400 mg/day Dasatinib
NUMBER REGISTERED
253 127 126
INELIGIBLE 5 2 3 ELIGIBLE 248 125 123 Not Analyzable 2 2 0 RESPONSE ASSESSMENT Determinable 231 118 113 Not Determinable 15 5 10 ADVERSE EVENT ASSESSMENT Evaluable 245 123 122 Not Evaluable 1 0 1
Patient Characteristics
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
Imatinib 400 mg/day Dasatinib
(n=123) (n=123)
AGE Median
50.7
47.7
Minimum 19.6 18.5 Maximum 89.1 90.8 SEX Males
72
59% 75
61%
Females 51 41% 48 39% HISPANIC Yes
1
1% 6
5%
No 82 67% 72 59% Unknown 40 33% 45 37% RACE White
85
69% 75
61%
Black 3 2% 2 2% Asian 3 2% 2 2% Pacific Islander 0 0% 1 1% Native American 1 1% 0 0% Multi-Racial 1 1% 3 2% Unknown 30 24% 40 33% HASFORD RISK CATEGORY Low
44
36% 44
36%
Intermediate 45 37% 40 33% High 34 28% 39 32%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 18
S0325/IIB
Treatment Summary
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
TOTAL
Imatinib
400 mg/day Dasatinib
NUMBER ON PROTOCOL TREATMENT
136 57 79
NUMBER OFF PROTOCOL TREATMENT 110 66 44 REASON OFF TREATMENT Treatment completed as planned 23 17 6 Adverse Events or side effects 34 15 19 Refusal unrelated to adverse events 13 8 5 Progression/relapse 5 4 1 Death 3 2 1 Other - not protocol specified 32 20 12 Reason under review 0 0 0MAJOR PROTOCOL DEVIATIONS 3 0 3
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 19
S0325/IIB
Number of Patients with a Given Type and Grade of Adverse Event
Imatinib 400 mg/day versus Dasatinib
Adverse Events Unlikely or Not Related to Treatment Excluded
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Data as of February 9, 2011
Imatinib
400 mg/day
Dasatinib
(n=123) (n=122)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ≤ 2 3 4 5
ALT
120 3 0 0 121 1 0 0
AST 121 2 0 0 121 1 0 0Blurred vision 123 0 0 0 121 1 0 0Bronchospasm 122 1 0 0 122 0 0 0CNS ischemia 123 0 0 0 121 1 0 0CPK 123 0 0 0 121 1 0 0Cardiac ischemia/infarction 123 0 0 0 120 1 1 0Colitis 123 0 0 0 120 2 0 0Cond. Abn.: Asystole 123 0 0 0 121 0 1 0Constipation 123 0 0 0 121 1 0 0Dehydration 123 0 0 0 121 1 0 0Diarrhea 121 2 0 0 116 6 0 0Dizziness 122 1 0 0 122 0 0 0Dyspnea 121 2 0 0 115 7 0 0Edema-head and neck 121 2 0 0 122 0 0 0Edema-limb 122 1 0 0 121 1 0 0Fatigue 122 1 0 0 121 1 0 0Febrile neutropenia 123 0 0 0 119 1 2 0GI Pain: abdomen 122 1 0 0 120 2 0 0Hemoglobin 118 5 0 0 110 11 1 0Hot flashes 123 0 0 0 121 1 0 0Hyperglycemia 123 0 0 0 119 3 0 0Hyperkalemia 123 0 0 0 121 1 0 0Hypernatremia 123 0 0 0 121 1 0 0Hypertension 123 0 0 0 121 1 0 0Hypokalemia 121 2 0 0 121 1 0 0Hypophosphatemia 122 1 0 0 121 1 0 0Inf, 3-4 ANC: blood 123 0 0 0 121 1 0 0Left vent. diastolic dysfunct. 123 0 0 0 121 1 0 0Leukocytes 120 3 0 0 119 2 1 0Lung Inf, 0-2 ANC: lung 123 0 0 0 120 2 0 0Lung Inf, 0-2 ANC: sinus 123 0 0 0 121 1 0 0Lung Inf, 3-4 ANC: lung 123 0 0 0 120 2 0 0Lung Inf, Unk ANC: sinus 123 0 0 0 121 1 0 0Lung Pain: chest/thorax 122 1 0 0 121 1 0 0Lymphopenia 122 1 0 0 119 3 0 0Metabolic/Lab-other 123 0 0 0 121 0 1 0Mucositis, clin: oral cavity 121 2 0 0 122 0 0 0Musculo. Pain: back 122 1 0 0 122 0 0 0Musculo. Pain: bone 123 0 0 0 121 1 0 0Musculo. Pain: joint 121 2 0 0 121 1 0 0Musculo. Pain: muscle 122 1 0 0 122 0 0 0Nausea 122 1 0 0 122 0 0 0Neuro Pain: head/headache 120 3 0 0 119 3 0 0Neuropathy-motor 123 0 0 0 121 1 0 0Neuropathy-sensory 123 0 0 0 121 0 1 0Neutrophils 108 14 1 0 104 13 5 0Pain-other 122 1 0 0 122 0 0 0Pericardial effusion 123 0 0 0 119 2 1 0Platelets 113 8 2 0 100 13 9 0Pleural effusion 122 1 0 0 119 3 0 0Prolonged QTc 123 0 0 0 121 1 0 0Pruritus 121 2 0 0 122 0 0 0Pulmonary-other 123 0 0 0 121 1 0 0Rash 121 2 0 0 122 0 0 0Retinal detachment 122 1 0 0 122 0 0 0Sex/Rep Inf, 0-2 ANC: scrotum
123 0 0 0 121 1 0 0
Vaginal mucositis 123 0 0 0 121 1 0 0Vomiting 123 0 0 0 121 1 0 0Watery eye 123 0 0 0 121 1 0 0Weight gain 123 0 0 0 120 2 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Number
80 41 2 0 54 51 17 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 20
S0325/IIB
Hematologic Response
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
Imatinib
400 mg/day Dasatinib
Complete Response
100 81% 100 81%
Unconfirmed Complete Response 12 10% 7 6%Stable/No Response 6 5% 6 5%Increasing Disease 0 0% 0 0%Assessment Inadequate 5 4% 10 8% Total
123 100% 123 100%
Overall Survival by Treatment Arm
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
0%
20%
40%
60%
80%
100%
0 12 24 36 48
Months since Complete Remission
Imatinib 400 mg/day
Dasatinib
At Risk
123
123
Deaths
4
3
2-Year
Estimate
98%
97%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 21
S0325/IIB
Relapse-Free Survival by Treatment Arm
Imatinib 400 mg/day versus Dasatinib
Data as of February 9, 2011
0%
20%
40%
60%
80%
100%
0 12 24 36 48
Months since Complete Remission
Dasatinib
Imatinib 400 mg/day
At Risk
107
112
Failed
4
7
2-Year
Estimate
96%
95%
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 22
S0521/III
S0521 Phase III
Coordinating Group: SWOG
A Randomized Trial of Maintenance Versus Observation for Patients with
Previously Untreated Low and Intermediate Risk Acute Promyelocytic
Leukemia (APL), Phase III
Participants: SWOG, CTSU (endorsed by ECOG and CALGB)
Study Coordinators: S Coutre, D Persons, C Willman
Statisticians: K Kopecky, H Gundacker
Data Coordinator: T Maher
Date Activated: 6/1/2007
Date Closed: 5/27/2010
Schema
R E G I S T R A T I O N
Observation: No therapy
R E G I S T R A T I O N
ATRA, Dauno- rubicin, Ara-C
Arsenic Trioxide (2 cycles)
Induction
Gemtuzumab
Ozogamicin
CR, CRi or PR
ATRA, Dauno- rubicin, (2 cycles)
CR or CRi R
E G I S T
R A T I O N
not CRm
CRm
Consolidation #1 and #2
Consolidation #3 and #4
R A N
D O M I Z E
Post-Consolidation
Maintenance: ATRA, 6-MP, MTX
- The study design was revised on August 15, 2010: See the Summary Statement for details.
Objectives To compare disease-free survival (DFS) among
patients with previously untreated low and inter-mediate risk APL who are PCR-negative for
PML-RARα after consolidation therapy and re-
ceive maintenance therapy versus patients who
receive no maintenance therapy.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 23
S0521/III
To assess toxicities of induction, consolidation
and maintenance therapies.
To test whether gene expression profiles assessed
prior to treatment are predictive of resistance to remission induction chemotherapy, correlate with
detectable minimal residual disease post-
consolidation, and predict relapse-free survival in
patients who respond to induction chemotherapy.
To investigate in a preliminary manner the out-
comes of patients who fail to achieve or maintain
PCR-negativity after consolidation therapy, when
treated with gemtuzumab ozogamicin.
Patient Population Patients must have a morphologically confirmed
diagnosis of low or intermediate risk acute pro-
myelocytic leukemia (APL), or the variant form
of APL, based on bone marrow or peripheral
blood examination performed within 14 days be-
fore registration. The WBC and platelet count
confirming low or intermediate risk must be ob-
tained within 48 hours before registration, with
the following exception: if the patient received
ATRA before registration, this WBC and platelet count must be obtained within 48 hours before
ATRA was started. Patients who are known to be
PML-RARα-negative by the RT-PCR assay are
not eligible. Patients with recurrent disease are
not eligible.
Patients must not have received systemic chemo-
therapy, hydroxyurea, or leukapheresis for acute
leukemia, with the exception of ATRA at a dose
of ≤ 45 mg/m2/day for ≤ 5 days before registra-
tion. Patients must not have received more than one dose of intrathecal chemotherapy for acute
leukemia. Since patients must have low or inter-
mediate risk APL to be eligible for the study, the
use of hydroxyurea or leukapheresis will not be
necessary and is prohibited.
Patients must be 18 years old or older, and must
have a Zubrod performance status of 0, 1, 2, or 3.
Patients with unstable cardiac arrhythmias or un-
stable angina are not eligible.
Stratification/Descriptive Factors At the post-consolidation randomization, patients
who are in CRm will be stratified by (1) age: 18-
60 vs > 60 years, (2) APL risk group: low vs in-
termediate, and (3) Did the patient receive con-
solidation cycle 3 or 4 (ATRA plus daunorubi-
cin): Yes vs No.
Accrual Goals The accrual goal of this study is 400 eligible pa-
tients (200 per arm) randomized to step 3 (post-
consolidation). If 80% of patients registered to
the first step are randomized, the total accrual to
the study will be 500 patients.
Summary Statement The study was closed to entry of new patients on
May 27, 2010 due to inadequate accrual. Effec-
tive August 15, 2010 patients proceeding to post-
consolidation therapy were no longer registered
to gemtuzumab therapy and all eligible patients, regardless of molecular response, were non-
randomly assigned to receive post-consolidation
chemotherapy.
A total of 105 patients were accrued to the induc-
tion registration. None are known to be ineligible.
Four patients were taken off protocol induction
therapy due to the following toxicities: unre-
solved renal failure, pneumonia with Grade 4
neutropenia, pseudotumor cerebri, and ATRA
syndrome. One patient withdrew consent on Day 30 of induction.
All 105 patients were evaluated for induction tox-
icities. One patient suffered a fatal toxicity (typh-
litis). Grade 4 non-hematologic toxicities were
reported for another 22 patients including three
with retinoic acid syndrome or APL differentia-
tion syndrome, one with DIC, and one with both
retinoic acid syndrome or APL differentiation
syndrome and DIC.
One hundred four patients have been evaluated
for response and 79 patients achieved complete
response (76%, 95% CI 67%-84%), one of whom
was with incomplete blood count recovery. Only
one patient had resistant disease. Seven of the
105 patients have died for a one-year survival rate
of 93% (95% CI 88%-98%). One patient relapsed
from CR after completing consolidation therapy
but before registration to post-consolidation. No
other patients have had reports of clinical relapse.
Ninety-two patients were registered for consoli-
dation therapy. One major protocol deviation was
reported for a patient who received extra ATRA
and daunorubicin in error for the third consolida-
tion cycle. This patient came off protocol consol-
idation treatment for that reason. Another patient
was taken off consolidation therapy by the treat-
ing physician before starting daunorubicin due to
HIV-related frailty. Six additional patients came off consolidation therapy due to toxicity: one for
pericardial effusion with pericarditis during the
first consolidation cycle, one for sepsis after the
first cycle, one each for thrombocytopenia and
reduced ejection fraction after the second cycle,
one for severe headache during the third cycle,
and one for neuropathy after the third cycle. One
death (cardiac dysfunction) was reported during
consolidation therapy and was reported as possi-
bly attributable to protocol treatment. Grade 4
non-hematologic toxicities were reported for five
additional patients during consolidation: one each with infection and pericardial effusion during the
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 24
S0521/III
first consolidation cycle, one with infection and
elevated LFTs during the second cycle, one with
infection during the third cycle, and one with car-
diac dysfunction during the fourth cycle.
Sixty-five patients were registered to post-
consolidation therapy, 55 were randomized and
ten were non-randomly assigned to post-
consolidation chemotherapy after the study de-
sign revision. Three major protocol deviations
were reported for patients who were randomized
to receive post-consolidation therapy but refused
treatment. A fourth patient refused after starting
post-consolidation therapy. Two patients came
off post-consolidation therapy due to toxicity: one
due to severe headache and fatigue and one due
to headache, fever, nausea, vomiting and dysp-
nea.
Of the 27 patients evaluated for post-
consolidation toxicities, no fatal toxicities have been reported. Grade 4 non-hematologic toxici-
ties (elevated LFTs) were reported for one patient
during post-consolidation therapy.
One patient was registered to post-consolidation
gemtuzumab therapy before the registration was
closed to accrual due to the study design revision.
There have been no reports of fatal or Grade 4
non-hematologic toxicities for this patient. No pa-
tients registered to post-consolidation therapy
have relapsed and one patient died without a re-port of relapse.
Initial Registrations By 3 Month Intervals
0
10
20
Time of Registration
OCTDEC2007
3
JANMAR2008
4
APRJUN2008
8
JULSEP2008
2
OCTDEC2008
9
JANMAR2009
14
APRJUN2009
11
JULSEP2009
13
OCTDEC2009
18
JANMAR2010
13
APRJUN2010
10
ATRA + ARA-C + Daunorubicin
Registration by Institution
Institutions Total
Reg Institutions Total
Reg
CALGB
47 MUSC, Hollings CC
1ECOG 28 New Mexico MBCCOP 1Stanford University 9 Puget Sound 1Michigan, U of 4 Southeast CCC CCOP 1Loyola University 3 Tulane University 1Rochester, Univ of 3 Utah, U of 1
Wichita CCOP 3 Wayne State Univ 1
Central IL CCOP 1 Total (15 Institutions) 105
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 25
S0521/III
Registration, Eligibility, and Evaluability
Data as of February 22, 2011
ATRA
+ ARA-C +
Daunorubicin
ATRA
+ ARA-C +
Daunorubicin
NUMBER REGISTERED
105 ADVERSE EVENT ASSESSMENT
ELIGIBLE 105 Evaluable 105 RESPONSE ASSESSMENT Determinable 95 Not Determinable 9 Too Early 1
Patient Characteristics
Data as of February 22, 2011
ATRA + ARA-C +
Daunorubicin
ATRA + ARA-C +
Daunorubicin
(n=105) (n=105)
AGE RACE
Median 49.1 White 87 83% Minimum 20.5 Black 8 8% Maximum 82.4 Asian 7 7% Native American 1 1%SEX Unknown 2 2% Males 61 58% Females 44 42% HISPANIC Yes 6 6% No 87 83% Unknown 12 11%
Treatment Summary
Induction
Data as of February 22, 2011
ATRA
+ ARA-C +
Daunorubicin
NUMBER ON PROTOCOL TREATMENT
0
NUMBER OFF PROTOCOL TREATMENT 105 REASON OFF TREATMENT Treatment completed as planned 96 Adverse Events or side effects 4 Refusal unrelated to adverse events 1 Progression/relapse 0 Death 3 Other - not protocol specified 0 Reason under review 1MAJOR PROTOCOL DEVIATIONS 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 26
S0521/III
Number of Patients with a Given Type and Grade of Adverse Event
Induction
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Data as of February 22, 2011
ATRA + ARA-C +
Daunorubicin
ATRA + ARA-C +
Daunorubicin
(n=105) (n=105)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ADVERSE EVENT ≤ 2 3 4 5
ALT
100 5 0 0
Inf, 0-2 ANC: blood
104 0 1 0
AST 103 2 0 0 Inf, 3-4 ANC: blood 95 10 0 0Acidosis 104 0 1 0 Infection-other 103 2 0 0Alkaline phosphatase 104 1 0 0 Lung Hemorrhage: lung 104 0 1 0Alkalosis 103 1 1 0 Lung Hemorrhage: nose 103 2 0 0Anorexia 101 4 0 0 Lung Inf, 3-4 ANC: lung 97 8 0 0Bilirubin 98 7 0 0 Lung Inf, 3-4 ANC: up. aero. 104 1 0 0CNS hemorrhage 104 1 0 0 Lung Inf, Unk ANC: lung 104 1 0 0CPK 103 1 1 0 Metabolic/Lab-other 104 1 0 0Cardiac Arrhythmia-other 104 1 0 0 Mood alteration: agitation 104 1 0 0Cardiac troponin T 103 1 1 0 Mood alteration: depression 104 1 0 0Cholesterol 104 0 1 0 Mucositis, clin: oral cavity 102 3 0 0Coagulation-other 103 2 0 0 Mucositis, clin: rectum 104 1 0 0Confusion 101 4 0 0 Muscle weakness: low. extrem. 104 1 0 0Creatinine 103 1 1 0 Muscle weakness: up. extrem. 104 1 0 0DIC 94 9 2 0 Muscle weakness: whole body 103 1 1 0Diarrhea 94 11 0 0 Musculo. Pain: back 103 2 0 0Distension 103 2 0 0 Musculo. Pain: limb 104 1 0 0Dizziness 104 1 0 0 Musculo. Pain: muscle 102 1 2 0Dry skin 104 1 0 0 Musculo. Pain: neck 104 1 0 0Dyspnea 94 9 2 0 Myositis 103 1 1 0Enteritis 104 1 0 0 Nausea 99 6 0 0Fatigue 97 8 0 0 Neuro Pain: head/headache 95 10 0 0Febrile neutropenia 47 52 6 0 Neuropathy-motor 104 1 0 0Fever 104 1 0 0 Pericardial effusion 104 0 1 0GI Hemorrhage: rectum 104 1 0 0 Petechiae 103 2 0 0GI Inf, 3-4 ANC: cecum 104 1 0 0 Photosensitivity 104 1 0 0GI Inf, 3-4 ANC: colon 102 3 0 0 Pleural effusion 104 0 1 0GI Inf, 3-4 ANC: gums 104 1 0 0 Prolonged QTc 102 3 0 0GI Inf, 3-4 ANC: tooth 104 1 0 0 Rash 102 3 0 0GI Inf, Unk ANC: gums 104 1 0 0 Renal failure 99 5 1 0GI Inf, Unk ANC: rectum 104 1 0 0 Renal-other 104 0 1 0GI Pain: abdomen 102 3 0 0 Retinal detachment 104 0 1 0GU Hemorrhage: vagina 104 1 0 0 Retinoic acid syndrome 92 9 4 0GU Inf, 3-4 ANC: UTI 104 1 0 0 Sexual/Repro. Pain: scrotum 104 1 0 0GU Inf, Unk ANC: bladder 104 1 0 0 Skin Inf, 0-2 ANC: skin 102 3 0 0Gait/walking 104 0 1 0 Skin Inf, 3-4 ANC: skin 102 3 0 0Hep Inf, 0-2 ANC: gallbladder 104 1 0 0 Skin Inf, Unk ANC: skin 104 1 0 0Hyperglycemia 101 4 0 0 Syncope 102 3 0 0Hypertension 102 3 0 0 Thrombosis/embolism 104 1 0 0Hypertriglyceridemia 100 4 1 0 Typhlitis 102 1 1 1Hypoalbuminemia 101 4 0 0 Vasovagal episode 104 1 0 0Hypocalcemia 102 2 1 0 Vent Arrhyth: Vent Tachy. 104 0 1 0Hypokalemia 101 4 0 0 Vomiting 104 1 0 0Hyponatremia 101 4 0 0 Weight gain 104 1 0 0Hypophosphatemia 98 7 0 0 Hypotension 104 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Hypoxia 99 5 1 0 Number 14 68 22 1
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 27
S0521/III
Response
Initial Registration
Data as of February 22, 2011
ATRA + ARA-C
+ Daunorubicin
Complete Response
78 75%
CR w/Incomplete Hem. Recovery 1 1%Partial Response 15 14%Assessment Inadequate 7 7%Resistant Disease 1 1%Died <7 Days After 1st Course 2 2% Total
104 100%
Overall Survival by Treatment Arm
Initial Registration
Data as of February 22, 2011
0%
20%
40%
60%
80%
100%
0 12 24 36
Months After Registration
ATRA + ARA-C + Daunorubicin
At Risk
105
Deaths
7
1-Year
Estimate
93%
Registration, Eligibility, and Evaluability
Consolidation
Data as of February 22, 2011
Consolidation Consolidation
NUMBER REGISTERED
92 ADVERSE EVENT ASSESSMENT
ELIGIBLE 92 Evaluable 88 Too Early 4
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 28
S0521/III
Treatment Summary
Consolidation
Data as of February 22, 2011
Consolidation
NUMBER ON PROTOCOL TREATMENT
5
NUMBER OFF PROTOCOL TREATMENT 87 REASON OFF TREATMENT Treatment completed as planned 79 Adverse Events or side effects 6 Refusal unrelated to adverse events 0 Progression/relapse 0 Death 0 Other - not protocol specified 2 Reason under review 0MAJOR PROTOCOL DEVIATIONS 1
Number of Patients with a Given Type and Grade of Adverse Event
Consolidation
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Data as of February 22, 2011
Consolidation Consolidation
(n=88) (n=88)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ADVERSE EVENT ≤ 2 3 4 5
ALT
85 2 1 0
Mood alteration: anxiety
87 1 0 0
AST 86 1 1 0 Mucositis, funct: oral cav. 87 1 0 0Anorexia 87 1 0 0 Musculo. Pain: joint 84 4 0 0Dehydration 87 1 0 0 Musculo. Pain: limb 87 1 0 0Dysphagia 87 1 0 0 Musculo. Pain: muscle 86 2 0 0Fatigue 83 5 0 0 Nausea 84 4 0 0Febrile neutropenia 80 7 1 0 Neuro Pain: head/headache 85 3 0 0Fever 87 1 0 0 Neuropathy-sensory 86 2 0 0Flu-like syndrome 87 1 0 0 Opportunistic infection 87 1 0 0GI Pain: abdomen 87 1 0 0 Pericardial effusion 87 0 1 0GI Pain: rectum 87 1 0 0 Pericarditis 87 1 0 0Hyperglycemia 84 4 0 0 Pneumonitis 87 0 1 0Hypertension 87 1 0 0 Prolonged QTc 82 6 0 0Hypertriglyceridemia 87 1 0 0 Rash 87 1 0 0Hyperuricemia 87 1 0 0 Renal failure 87 1 0 0Hypocalcemia 87 1 0 0 Restrictive cardiomyopathy 87 1 0 0Hypophosphatemia 87 1 0 0 Skin Inf, 0-2 ANC: skin 87 1 0 0Hypotension 86 1 1 0 Vasovagal episode 87 1 0 0Inf, 0-2 ANC: blood 83 3 2 0 Vent Arrhyth: Vent Tachy. 87 1 0 0Inf, 0-2 ANC: cath.-related 87 1 0 0 Vomiting 87 1 0 0Inf, 3-4 ANC: blood 87 1 0 0 Left vent. systolic dysfunct. 85 1 1 1 MAXIMUM GRADE ANY ADVERSE EVENT Lung Pain: chest/thorax 86 2 0 0 Number 51 31 5 1Lung Pain: throat/phar/lar 87 1 0 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 29
S0521/III
Registration, Eligibility, and Evaluability
Post-Consolidation: Chemotherapy or Observation
Data as of February 22, 2011
TOTAL
ATRA
+ 6MP +
MTX Observation
NUMBER REGISTERED
65 38 27
ELIGIBLE 65 38 27 ADVERSE EVENT ASSESSMENT Evaluable 27 27 0 Not Evaluable 3 3 0 Too Early 8 8 0 Not Applicable 27 0 27
Treatment Summary
Post-Consolidation: Chemotherapy or Observation
Data as of February 22, 2011
ATRA
+ 6MP +
MTX
NUMBER ON PROTOCOL TREATMENT
21
NUMBER OFF PROTOCOL TREATMENT 17 REASON OFF TREATMENT Treatment completed as planned 9 Adverse Events or side effects 2 Refusal unrelated to adverse events 4 Progression/relapse 0 Death 1 Other - not protocol specified 0 Reason under review 1MAJOR PROTOCOL DEVIATIONS 3
Number of Patients with a Given Type and Grade of Adverse Event
Post-Consolidation: Chemotherapy or Observation
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Data as of February 22, 2011
ATRA + 6MP +
MTX
ATRA + 6MP +
MTX
(n=27) (n=27)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ADVERSE EVENT ≤ 2 3 4 5
ALT
26 0 1 0
Nausea
26 1 0 0
AST 26 0 1 0 Neuro Pain: head/headache 23 4 0 0Fatigue 26 1 0 0 Pruritus 26 1 0 0Hypertriglyceridemia 26 1 0 0 Left vent. systolic dysfunct. 26 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Mucositis, clin: oral cavity 26 1 0 0 Number 19 7 1 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 30
S0535/II
S0535 Phase II
Coordinating Group: SWOG
A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin
in Patients with Previously Untreated High-Risk Acute Promyelocytic
Leukemia
Participants: SWOG, CTSU (endorsed by ECOG and CALGB)
Study Coordinators: J Lancet, R Komrokji, C Willman, M Slovak
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 11/15/2007
Schema
R
E G I S T R A T I O
N
Induction Consolidation 1 and 2
ATRA + Gemtuzumab ozogamicin + Arsenic trioxide
CR Arsenic trioxide (2 cycles)
if remain in CR
Consolidation 3 and 4
ATRA + Daunomycin (2 cycles)
if remain in CR
Gemtuzumab ozogamicin (1 dose/month for 2 months)
Consolidation 5 and 6
if remain in CR
ATRA + 6-MP + Methotrexate (for 1 year)
Maintenance
Objectives To assess the event-free survival and death during
the first six weeks in patients with previously un-
treated high-risk acute promyelocytic leukemia
treated with a combined regimen of all trans reti-noic acid (ATRA), arsenic trioxide, and gemtu-
zumab ozogamicin.
To estimate the frequency and severity of toxici-
ties of this regimen in this group of patients.
To investigate the molecular response rate utiliz-ing this regimen in high-risk patients.
Patient Population Patients must have a morphologically confirmed
diagnosis of high-risk acute promyelocytic leu-
kemia (APL), based on bone marrow examination
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 31
S0535/II
performed within 14 days before registration. The
WBC confirming high-risk status must be ob-
tained within 24 days of registration. Patients
who are known to be PML-RARα negative by
RT-PCR assay are not eligible.
Patients must not have received prior systemic
chemotherapy for acute leukemia, with the excep-
tion of ATRA, which may be administered for up
to three days prior to registration. Administration
of hydroxyurea, corticosteroids, or leukapheresis
to control high cell counts prior to registration is
permitted.
Patients must have reached their 18th birthday.
Patients with prolonged QTc > 0.47 seconds are not eligible.
Accrual Goals Initially, 32 eligible patients will be accrued. If
more than seven of these patients die within the
first six weeks, the study will be closed. Other-
wise, 38 additional eligible patients will be ac-
crued for a total of 70 eligible patients. Patients
enrolled before RT-PCR results are known and
who are subsequently found to be negative for PML-RARα will not be counted towards these
goals.
Summary Statement The study was temporarily closed to accrual on
June 22, 2010 and re-activated on January 4,
2011 when an alternative gemtuzumab supply be-
came available. In addition, the criteria have been
met for continuation to complete accrual.
As of December 31, 2010, a total of 34 patients have been accrued. Two patients are ineligible
and excluded from the following analysis: one
patient was PML-RARα negative by FISH and
one patient did not have high-risk APL. Two pa-
tients who did not receive protocol therapy after
registration are also excluded: one patient was
found to be PML-RARα negative by cytogenetics
and FISH and another who was hospitalized for
transfusions after registration. One patient was
removed from protocol therapy after one month
due to lack of insurance coverage.
No fatal toxicities have been reported for the 27
patients evaluated for induction toxicities. Grade
4 non-hematologic induction toxicities were re-
ported for two patients: one with sensory neuro-
pathy and one with prolonged QTc, dyspnea, and
elevated creatinine.
Grade 4 febrile neutropenia was reported for one
patient during consolidation therapy. There have been no other reports of Grade 4 or higher non-
hematologic toxicities during consolidation. In
addition, no fatal or Grade 4 non-hematologic
toxicities have been reported for patients on
maintenance therapy.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg
CALGB
15
ECOG 8Stanford University 3MUSC, Hollings CC 2Wichita CCOP 2Grand Rapids CCOP 1Loyola University 1Puget Sound 1
Utah, U of 1
Total (9 Institutions) 34
Registration, Eligibility, and Evaluability
Registrations ending December 31, 2010; Data as of March 2, 2011
ATRA + G.O.
+ Arsenic
ATRA + G.O.
+ Arsenic
NUMBER REGISTERED
34 ADVERSE EVENT ASSESSMENT
INELIGIBLE 2 Evaluable 27 ELIGIBLE 32 Too Early 3 Not Analyzable 2
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 32
S0535/II
Patient Characteristics
Registrations ending December 31, 2010; Data as of March 2, 2011
ATRA + G.O. + Arsenic ATRA + G.O. + Arsenic
(n=30) (n=30)
AGE HISPANIC
Median 45.3 Yes 1 3% Minimum 21.2 No 25 83% Maximum 69.6 Unknown 4 13% SEX RACE Males 10 33% White 27 90% Females 20 67% Black 2 7% Pacific Islander 1 3%
Treatment Summary
Induction
Registrations ending December 31, 2010; Data as of March 2, 2011
ATRA + G.O.
+ Arsenic
NUMBER ON PROTOCOL TREATMENT
2
NUMBER OFF PROTOCOL TREATMENT 28 REASON OFF TREATMENT Treatment completed as planned 25 Adverse Events or side effects 0 Refusal unrelated to adverse events 1 Progression/relapse 0 Death 1 Other - not protocol specified 0 Reason under review 1MAJOR PROTOCOL DEVIATIONS 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 33
S0535/II
Number of Patients with a Given Type and Grade of Adverse Event
Induction
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Registrations ending December 31, 2010; Data as of March 2, 2011
ATRA
+ G.O. + Arsenic
ATRA
+ G.O. + Arsenic
(n=27) (n=27)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ADVERSE EVENT ≤ 2 3 4 5
ALT
23 4 0 0
Hypocalcemia
26 1 0 0
ARDS 26 1 0 0 Hypokalemia 22 5 0 0AST 24 3 0 0 Hyponatremia 26 1 0 0Anorexia 25 2 0 0 Hypophosphatemia 23 4 0 0Bilirubin 26 1 0 0 Hypoxia 25 2 0 0Confusion 26 1 0 0 Left vent. systolic dysfunct. 26 1 0 0Constipation 25 2 0 0 Lung Inf, 3-4 ANC: lung 26 1 0 0Creatinine 26 0 1 0 Muscle weakness: whole body 25 2 0 0DIC 25 2 0 0 Musculo. Pain: muscle 26 1 0 0Diarrhea 26 1 0 0 Nausea 25 2 0 0Dyspnea 25 1 1 0 Neuro Pain: head/headache 24 3 0 0Fatigue 24 3 0 0 Neuropathy-sensory 26 0 1 0Febrile neutropenia 17 10 0 0 PTT 26 1 0 0Fever 26 1 0 0 Prolonged QTc 22 4 1 0Fibrinogen 26 1 0 0 Rash 26 1 0 0GFR 26 1 0 0 Somnolence 26 1 0 0GU Inf, 0-2 ANC: UTI 26 1 0 0 Syncope 26 1 0 0Hyperglycemia 22 5 0 0 Syndromes-other 26 1 0 0Hypermagnesemia 25 2 0 0 Weight Loss 26 1 0 0Hypertension 24 3 0 0 Hyperuricemia 26 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Hypoalbuminemia 26 1 0 0 Number 8 17 2 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 34
S0703/II
S0703 Phase II
A Phase II Trial of Azacitidine (NSC-102816) Plus Gemtuzumab
Ozogamicin as Induction and Post-Remission Therapy in Patients of Age 60
and Older with Previously Untreated Non-M3 Acute Myeloid Leukemia
Study Coordinators: S Nand, J Godwin, C Willman, T Norwood
Statisticians: H Gundacker, K Kopecky
Data Coordinator: C White
Date Activated: 12/1/2008
Schema
R E G I S T E R
Induction Consolidation
Azacitidine + Gemtuzumab (1 or 2 cycles)
CR or CRi*
Azacitidine + Gemtuzumab (1 cycle)
Azacitidine (4 cycles)
*CRi: Morphologic complete remission with incomplete blood count recovery
Maintenance
CR or CRi*
Objectives To test whether outcomes of patients of age 60 or
older with previously untreated non-M3 acute
myeloid leukemia treated with azacitidine plus
gemtuzumab ozogamicin are sufficient to warrant
Phase III investigation. This will be tested inde-pendently in two groups of patients: (1) good risk
patients, defined as those of age 60-69 years or
with a Zubrod performance status 0-1, and (2)
poor risk patients, defined as those who are at
least 70 years old and have a Zubrod performance
status 2-3.
To estimate the frequency and severity of toxici-
ties of this regimen in the good and poor risk
groups of patients.
To investigate in a preliminary manner the dis-
ease-free survival of patients who achieve com-
plete remission and receive post-remission thera-
py on this study.
To investigate in a preliminary manner the cyto-
genetic response rates of patients treated with this
regimen.
To investigate in a preliminary manner the effects
of cytogenetic abnormalities, promoter and global methylation changes and multidrug resistance on
overall survival and response to azacitidine plus
gemtuzumab ozogamicin therapy.
Patient Population Patients must have a morphologically confirmed
diagnosis of acute myeloid leukemia (AML) with
classification other than WHO acute promyelo-
cytic leukemia (FAB M3), based on bone marrow
examination performed within 14 days prior to registration. Patients with blastic transformation
of chronic myelogenous leukemia are not eligi-
ble.
Patients must not have received prior systemic
chemotherapy for acute leukemia. Administration
of hydroxyurea to control high WBC count prior
to registration is permitted. Patients with a history
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 35
S0703/II
of prior myelodysplastic syndrome (MDS) are el-
igible. However prior treatment of MDS with
AML induction-type chemotherapy or high dose
chemotherapy with hematopoietic stem cell sup-
port is not allowed. Patients may have received
hematopoietic growth factors, thalidomide, lena-lidomide, arsenic trioxide, signal transduction in-
hibitors and low dose cytarabine (< 100
mg/m2/day) for treatment of myelodysplastic
syndrome. Patients with previous therapy with
azacitidine, decitabine and gemtuzumab ozoga-
micin are not eligible. Patients must be off prior
therapy for MDS at least 30 days prior to study
registration and all toxicities must have resolved.
Patient must have a Zubrod performance status of
0, 1, 2, or 3 and have reached their 60th birthday. Patients with known hypersensitivity to azaciti-
dine, mannitol, hydroxyurea or gemtuzumab ozo-
gamicin are not eligible. Patients must have ade-
quate hepatic and renal function. Patients must
have an adequate cardiac function with left ven-
tricular ejection fraction of 40% or higher and no
clinical evidence of congestive heart failure. Pa-
tients with central nervous involvement are ex-
cluded. If central nervous involvement is clinical-
ly suspected, it must be ruled out by performing a
lumbar puncture. Patients not known to be HIV+ must be tested for HIV infection within 14 days
prior to registration. Patients who are HIV+ may
be eligible providing they meet all of the follow-
ing additional criteria: Patient must have no histo-
ry of AIDS defining events; CD4 cells ≥ 500
mm³; viral load of < 50 copies HIV mRNA/mm³
if on cART (combination antiviral therapy) or
<25,000 copies HIV mRNA if not on cART; no
zidovudine or stavudine as part of cART. Patients
who are HIV+ and do not meet all of these crite-
ria will not be eligible for this study. Patients with
other prior malignancies are not allowed except for the following: (a) adequately treated basal cell
or squamous cell skin cancer; or (b) any diagnosis
of malignancy made at least two years earlier, of
which there is no clinically evident cancer, and
for which the patient has completed all chemothe-
rapy and radiotherapy at least six months prior to
study registration.
Stratification/Descriptive Factors In order to allow outcomes to be investigated in-dependently between the good and poor risk
groups, patients will be stratified according to
risk status defined as follows: good risk patients
of age 60-69 or Zubrod performance status 0 or 1
vs poor risk patients of age 70 or older and Zu-
brod performance status 2 or 3.
Accrual Goals For the good risk group, initially, 30 eligible pa-
tients will be accrued. If fewer than twelve of
these patients achieve CR or CRi (complete re-
mission with incomplete blood count recovery) or
fewer than 23 survive more than 30 days, then the
study will be closed. Otherwise, 43 additional el-
igible good risk patients will be accrued for a to-
tal of 73 eligible good risk patients.
For the poor risk group, initially, 15 eligible pa-
tients will be accrued. If fewer than two of these
patients achieve CR or CRi (complete remission
with incomplete blood count recovery) or fewer
than eight patients survive more than 30 days,
then the study will be closed. Otherwise, 51 addi-
tional eligible poor risk patients will be accrued
for a total of 66 eligible poor risk patients.
Summary Statement The study was temporarily closed to accrual on
June 22, 2010 and re-activated on February 23,
2011 when an alternative gemtuzumab supply
was obtained. For both risk groups, the criteria
have been met for continuation to complete ac-
crual. As of December 31, 2010, a total of 90 pa-
tients have been accrued with 67 patients in the
good risk group and 23 patients in the poor risk
group.
Investigators are reminded to pay careful atten-
tion to the protocol definitions of good and poor
risk to ensure patients are correctly stratified.
1. Good Risk:
One patient, who did not start protocol treatment
because of an elevated WBC count, is not analyz-
able and is excluded from the analysis. Therefore, 66 good risk patients are included in this analysis.
One patient was taken off induction therapy after
two doses due to declining health status. One pa-
tient received the first induction cycle but not the
re-induction cycle due to elevated WBC count.
An additional patient who received the first cycle
of induction did not receive re-induction protocol
therapy due to toxicity (elevated LFTs).
Of the 62 patients evaluated for induction toxici-
ty, three deaths have been reported as possibly at-tributable to treatment: one due to infection and
two (disease progression and secondary malig-
nancy) are under review. Eight additional patients
had reports of Grade 4 non-hematologic toxici-
ties; two with infection, two with thrombo-
sis/embolism, and one each with atrial fibrilation
(coded as Cardiac Arrhythmia-other), cardiac
ischemia/infarction, hypocalcemia, anorexia and
muscle weakness, infection and increased biliru-
bin, and infection and dyspnea.
One good risk patient came off protocol mainten-
ance therapy after one cycle due to renal toxicity.
No Grade 4 or higher toxicities have been re-
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 36
S0703/II
ported for patients on consolidation or mainten-
ance therapy.
2. Poor Risk:
One poor risk patient who died before receiving
any protocol treatment is not analyzable and is
excluded from the analysis. Therefore, 22 poor
risk patients are included in this analysis. One pa-
tient was taken off protocol therapy due to toxici-
ty (COPD exacerbation) during the first induction
cycle. Another patient received the first induction
cycle but was not given re-induction due to pro-
gression not defined per protocol.
No fatal toxicities have been reported for the poor
risk patients. Four of the 22 patients evaluated for
induction toxicity had reports of Grade 4 non-
hematologic toxicities; three with infection and
one with hypotension and arrhythmia.
One poor risk patient came off protocol mainten-
ance therapy after two cycles due to neutropenia.
No Grade 4 or higher toxicities have been re-
ported for patients on consolidation or mainten-
ance therapy.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg Institutions Total
Reg
Loyola University
17 Wichita CCOP
4Michigan, U of 12 Kansas City CCOP 3Stanford University 11 Southeast CCC CCOP 3Kentucky, U of 9 Grand Rapids CCOP 2Central IL CCOP 5 Michigan CRC CCOP 2Columbia River CCOP 5 Mississippi, Univ of 1New Mexico MBCCOP 5 Montana CCOP 1
Wayne State Univ 5 St Joseph Med Ctr/So Calif, U of 1
Stormont-Vail Health/Kansas, U of 4 Total (17 Institutions) 90
Registration, Eligibility, and Evaluability
Classified by Risk Group
Registrations ending December 31, 2010; Data as of February 15, 2011
TOTAL Good risk Poor risk
NUMBER REGISTERED
90 67 23
ELIGIBLE 90 67 23 Not Analyzable 2 1 1 ADVERSE EVENT ASSESSMENT Evaluable 84 62 22 Too Early 4 4 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 37
S0703/II
Patient Characteristics
Classified by Risk Group
Registrations ending December 31, 2010; Data as of February 15, 2011
Good risk Poor risk
(n=66) (n=22)
AGE Median
70.6
75.2
Minimum 42.9 60.6 Maximum 88.5 88.7 SEX Males
37
56% 18
82%
Females 29 44% 4 18% HISPANIC Yes
3
5% 0
0%
No 54 82% 16 73% Unknown 9 14% 6 27% RACE White
64
97% 22
100%
Black 1 2% 0 0% Asian 1 2% 0 0%
Treatment Summary
Classified by Risk Group
Induction
Registrations ending December 31, 2010; Data as of February 15, 2011
TOTAL Good risk Poor risk
NUMBER ON PROTOCOL TREATMENT
0 0 0
NUMBER OFF PROTOCOL TREATMENT 88 66 22 REASON OFF TREATMENT Treatment completed as planned 79 60 19 Adverse Events or side effects 2 1 1 Refusal unrelated to adverse events 0 0 0 Progression/relapse 0 0 0 Death 1 1 0 Other - not protocol specified 3 2 1 Reason under review 3 2 1MAJOR PROTOCOL DEVIATIONS 0 0 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 38
S0703/II
Number of Patients with a Given Type and Grade of Adverse Event
Classified by Risk Group
Induction
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Registrations ending December 31, 2010; Data as of February 15, 2011
Good risk Poor risk
(n=62) (n=22)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ≤ 2 3 4 5
ALT
60 2 0 0 21 1 0 0
AST 60 2 0 0 22 0 0 0Anorexia 59 2 1 0 21 1 0 0Bilirubin 60 1 1 0 22 0 0 0CNS hemorrhage 61 1 0 0 22 0 0 0Cardiac Arrhythmia-other 61 0 1 0 22 0 0 0Cardiac ischemia/infarction 61 0 1 0 22 0 0 0Cardio. Pain: cardiac/heart 62 0 0 0 21 1 0 0Confusion 61 1 0 0 22 0 0 0Constipation 61 1 0 0 22 0 0 0Diarrhea 60 2 0 0 22 0 0 0Disease progression, NOS 60 0 0 2 22 0 0 0Dyspnea 61 0 1 0 21 1 0 0Edema-limb 61 1 0 0 22 0 0 0Eye Inf, 3-4 ANC: conjunct. 61 1 0 0 22 0 0 0Fatigue 56 6 0 0 18 4 0 0Febrile neutropenia 39 20 3 0 14 7 1 0GI Hemorrhage: upper GI 61 1 0 0 22 0 0 0GI Inf, 3-4 ANC: colon 62 0 0 0 21 1 0 0GI Inf, 3-4 ANC: tooth 59 3 0 0 22 0 0 0GU Inf, 3-4 ANC: UTI 60 2 0 0 21 1 0 0GU Inf, 3-4 ANC: kidney 62 0 0 0 21 0 1 0Hepatobiliary-other 61 1 0 0 22 0 0 0Hyperglycemia 58 4 0 0 19 3 0 0Hypertension 61 1 0 0 22 0 0 0Hypoalbuminemia 59 3 0 0 21 1 0 0Hypocalcemia 59 2 1 0 20 2 0 0Hypokalemia 57 5 0 0 22 0 0 0Hyponatremia 58 4 0 0 22 0 0 0Hypophosphatemia 58 4 0 0 22 0 0 0Hypotension 61 1 0 0 21 0 1 0Hypoxia 60 2 0 0 22 0 0 0Inf, 0-2 ANC: blood 61 1 0 0 22 0 0 0Inf, 3-4 ANC: blood 54 8 0 0 21 0 1 0Inf, 3-4 ANC: cath-related 61 1 0 0 21 1 0 0Infection-other 62 0 0 0 21 1 0 0Lung Inf, 3-4 ANC: lung 58 3 1 0 21 1 0 0Lung Inf, 3-4 ANC: sinus 60 1 0 1 22 0 0 0Mood alteration: depression 62 0 0 0 20 2 0 0Mucositis, funct: oral cav. 61 1 0 0 22 0 0 0Muscle weakness: whole body 60 1 1 0 21 1 0 0Petechiae 61 1 0 0 22 0 0 0Pleural effusion 62 0 0 0 21 1 0 0Pneumonitis 62 0 0 0 21 1 0 0Pulmonary-other 61 1 0 0 22 0 0 0Rash 61 1 0 0 22 0 0 0Secondary malignancy 61 0 0 1 22 0 0 0Skin Inf, 0-2 ANC: skin 61 1 0 0 22 0 0 0Skin Inf, 3-4 ANC: skin 58 4 0 0 22 0 0 0Skin Inf, Unk ANC: skin 61 1 0 0 22 0 0 0Supra Arrhyth: Atrial Fib. 61 1 0 0 21 0 1 0Thrombosis/embolism 60 0 2 0 22 0 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Number
18 33 8 3 8 10 4 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 39
S0805/II
S0805 Phase II Intergroup
Coordinating Group: SWOG
Phase II Study of Combination of Hyper-CVAD and Dasatinib (NSC-
732517) With or Without Allogeneic Stem Cell Transplant in Patients with
Philadelphia (Ph) Chromosome Positive and/or BCR-ABL Positive Acute
Lymphoblastic Leukemia (ALL)(A BMT Study)
Participants: SWOG, BMT CTN, CTSU (endorsed by ECOG and
CALGB)
Study Coordinators: F Ravandi, S O'Brien, S Forman, C Ha, J Wong, J Radich,
D Porter (BMT CTN)
Statisticians: H Gundacker, K Kopecky, M Othus
Data Coordinator: T Maher
Date Activated: 9/1/2009
Schema
R E G I S T R A T I O N
1
Single agent dasatinib
R E G I S T R A T I O N
3
Hyper-CVAD + dasatinib alternating
cycles with
High dose methotrexate, cytarabine + dasatinib
(total of 8 cycles)
Transplant ready?
CR
R E G I S T R A T I O N
2
Transplant
Yes
Induction/ consolidation:
Transplant ready?
R E G I S T R A T I O N
4
Maintenance: vincristine, prednisone + dasatinib interrupted on cycles 6 and 13 by Hyper-CVAD + dasatinib
No Yes
No
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 40
S0805/II
Objectives To test whether the relapse-free survival after al-
logeneic stem cell transplantation among Phila-
delphia chromosome positive and/or BCR/ABL
positive acute lymphoblastic leukemia (ALL) pa-
tients given an intensive short-term chemotherapy regimen of Hyper-CVAD in combination with the
tyrosine kinase inhibitor dasatinib is sufficiently
high to warrant further investigation.
To test whether the continuous complete remis-
sion rate for previously untreated Philadelphia
chromosome positive and/or BCR/ABL positive
acute lymphoblastic leukemia (ALL) patients
given an intensive short-term chemotherapy re-
gimen of Hyper-CVAD given in combination
with the tyrosine kinase inhibitor dasatinib is suf-ficiently high to warrant Phase III investigation.
To investigate in a preliminary manner the rela-
tive effectiveness of MRD detection using real-
time quantitative PCR for BCR/ABL versus flow
cytometry to predict the outcome of patients
treated by the hyper-CVAD + dasatinib regimen
and/or allogeneic stem cell transplant.
To estimate the frequency and severity of toxici-
ties of the intensive short-term chemotherapy re-
gimen in these patients.
To estimate the overall survival of all patients on
this study.
Patient Population Patients must have a morphologic diagnosis of
acute lymphoblastic leukemia (ALL), as defined in the protocol, with evidence of ALL involve-
ment in bone marrow and/or blood. Patients with
only extramedullary disease in the absence of
bone marrow or blood involvement are not eligi-
ble. Patients with M0 AML, mixed lineage leu-
kemia, or L3 (Burkitts) are not eligible for this
study. For ALL in marrow or peripheral blood,
immunophenotyping of the blood or marrow
lymphoblasts must be performed to determine li-
neage. Patients must be Philadelphia (Ph) chro-
mosome positive and/or BCR/ABL positive as confirmed by standard cytogenetics, FISH, and/or
polymerase chain reaction (PCR) testing per-
formed by a local laboratory.
Patients may have received no more than one
course of remission induction therapy for ALL,
providing this induction course was given prior to
the results of the cytogenetics testing for Ph
chromosome or BCR/ABL status being known.
Patients who have received any post-remission
therapy for ALL or who have relapsed from com-
plete remission are not eligible. Any prior induc-
tion chemotherapy must have been completed within 28 days prior to registration. For patients
who have received any prior therapy that was not
remission induction therapy, one of the following
must be true: at least six weeks must have elapsed
since any monoclonal antibodies were given, at
least seven days must have elapsed since any oth-
er treatment was given, and all toxicities of the
remission induction therapy must have resolved
to Grade ≤ 2; or the patient must have rapidly
progressive disease. For previously treated pa-
tients, the Study Coordinator must be contacted
before registration, in order to determine the re-gimen to be given in the first course of induc-
tion/consolidation therapy, based on prior thera-
py.
Patients must be at least 18 but no more than 50
years of age and must have Zubrod performance
status of 0, 1, or 2. Patients must not have active
pericardial effusion, ascites, or pleural effusion of
any grade, or prolonged QTc interval (QTc > 480
msec). Patients must not have prior history of known Type I hypersensitivity or anaphylactic
reactions to doxorubicin and must have adequate
renal and hepatic function.
Stratification/Descriptive Factors The patients will be stratified as follows: pre-
viously untreated vs achieved remission (CR or
CRi) vs refractory.
Accrual Goals Accrual will continue until 34 eligible patients
have received an allogeneic stem cell transplant.
It is anticipated that 85 eligible patients will need
to be registered to reach the accrual goal for the
transplanted patients.
Summary Statement This study was activated as of September 1, 2009.
On August 1, 2010, an amendment was activated
adding participation of BMT CTN and CTSU (endorsed by ECOG and CALGB) on this study.
As of December 31, 2010, one patient has been
accrued (through the CTSU from a CALGB insti-
tution).
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 41
S0910/II
S0910 Phase II
A Phase II Study of Epratuzumab (NSC-716711) in Combination with
Cytarabine and Clofarabine for Patients with Relapsed or Refractory Ph-
Negative Precursor B-Cell Acute Lymphoblastic Leukemia (ALL)
Study Coordinators: A Advani, S Coutre, J Radich
Statisticians: M Othus, H Gundacker
Data Coordinator: T Maher
Date Activated: 8/15/2010
Objectives To test whether the complete remission rate (CR
+ CRi) in patients with relapsed or refractory pre-
cursor B-cell acute lymphoblastic leukemia (ALL) is sufficiently high following treatment
with cytarabine, clofarabine, and epratuzumab to
warrant further investigation.
To estimate the frequency and severity of toxici-
ties associated with the dosing schedule of cyta-
rabine, clofarabine, and epratuzumab outlined by
this protocol.
To investigate in a preliminary manner the effect of minimal residual disease laboratory correlates
and cytogenetic factors on prognosis in this pa-
tient population.
Patient Population Patients must have a prior morphologic diagnosis
of precursor B-cell acute lymphoblastic leukemia
(ALL) (non T-cell) as defined in the protocol and
be either refractory to a standard induction regi-
men or have relapsed following successful prior induction therapy. Patients with M0 AML, mixed
lineage leukemia, or L3 (Burkitt's) are not eligi-
ble. Patients must have evidence of ALL in their
marrow or peripheral blood. At least 20% of mar-
row and/or peripheral blood lymphoblasts must
be CD22+ by flow cytometry from a sample col-
lected within 14 days prior to registration. Pa-
tients must have at least 5% lymphoblasts present
in the blood or bone marrow within 14 days prior
to registration. Patients must have a diagnosis of
Philadelphia chromosome-negative ALL. Patients
with unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are eligi-
ble for registration, but must be removed from
protocol therapy if found to be Ph+ or
BCR/ABL+ after registration.
Patients may have had any number or prior thera-
pies. Patients may have received prior allogeneic
or autologous bone marrow transplant. However,
patients who have received prior transplant (allo-geneic or autologous) will not be eligible if they
are still receiving immunosuppression therapy for
the treatment of graft versus host disease
(GvHD). Patients with prior allogeneic bone mar-
row transplant will be eligible only if both of the
following conditions are met: the transplant must
have been performed more than 90 days before
registration to this study, and the patient must not
have ≥ Grade 2 acute GvHD or either moderate or
severe limited chronic GvHD, or extensive chron-
ic GvHD of any severity. Patients must not have
received prior chemotherapy, any other investiga-tional agents, or have undergone any major sur-
gery within 14 days prior to registration, with the
following exceptions: hydroxyurea, which may
be administered concurrently with study drug un-
til the white blood count has come down to a rea-
sonable level as deemed by the treating physician,
maintenance therapy with steroids, vincristine,
and/or anti-metabolite agents, such as but not li-
mited to, mercaptopurine, thioguanine and me-
thotrexate. All drug-related toxicities must have
resolved to ≤ Grade 2. Patients less than 22 years of age must be willing to receive prophylactic in-
trathecal chemotherapy as defined in the protocol
while on study. Patients must not have received
previous treatment with clofarabine or epratuzu-
mab.
Patients must be at least 16 years of age and have
a Zubrod performance status of 0, 1, or 2. Patients
must not have active CNS involvement by clini-
cal evaluation. Patients with previous docu-
mented history of CNS involvement of ALL, or
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 42
S0910/II
with clinical signs or symptoms consistent with
CNS involvement of ALL must have a lumbar
puncture which is negative for CNS involvement
of ALL. Patients must undergo triplicate EKG
within 14 days prior to registration. Electrolytes
(K and Mg) should be corrected prior to the first EKG. For QTc > 500, the Study Coordinator
must be contacted to determine whether the pa-
tient will be eligible. Patients must not have a
systemic fungal, bacterial, viral, or other infection
that is not controlled. Patients must have adequate
renal and hepatic function. Patients must not have
≥ Grade 2 neuropathy (cranial, motor or sensory).
Patients known to be positive for HIV may be el-
igible but must be discussed with and approved
by the Study Coordinator prior to registration. Pa-
tients must not be pregnant or nursing because of
the teratogenic potential of the drug used in this
study.
Accrual Goals Initially, 20 eligible patients will be accrued. If
fewer than two patients achieve CR, the study
will be closed. Otherwise, 15 additional eligible
patients will be accrued for a total of 35 eligible
patients.
Summary Statement The study opened to accrual on August 15, 2010.
As of December 31, 2010, three patients have
been accrued (two from University of Utah and
one from University of Mississippi).
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 43
S0919/II
S0919 Phase II
A Phase II Study of Idarubicin and Ara-C in Combination with Pravastatin
for Relapsed Acute Myelogenous Leukemia (AML)
Study Coordinators: A Advani, E Copelan, C Willman
Statisticians: H Gundacker, M Othus
Data Coordinator: J Barce
Date Activated: 8/15/2009
Objectives To test whether the complete remission (CR) rate
(including CR with incomplete recovery [CRi]) in patients with relapsed acute myeloid leukemia
(AML) treated with a combination of chemothe-
rapy and pravastatin is sufficiently high to war-
rant Phase III investigation.
To estimate relapse-free survival and overall sur-
vival rates in this group of patients.
To estimate the frequency and severity of toxici-
ties of this regimen in this group of patients.
To evaluate in a preliminary manner whether
prestudy cytogenetic features correlate with re-
sponse in this group of patients.
Patient Population Patients must have a morphologically confirmed
diagnosis of acute myeloid leukemia (AML). Pa-
tients with acute promyelocytic leukemia (APL, FAB M3) or blastic transformation of chronic
myelogenous leukemia are not eligible.
Patients must have received at least one prior
chemotherapy regimen for their AML and they
may have received any type of chemotherapy.
They must have achieved complete remission,
lasting at least three months with their last induc-
tion regimen and they must have relapsed after
the last regimen. Relapse must be documented by
a bone marrow examination demonstrating > 5% blasts in the bone marrow not attributable to
another cause. Refractory patients and patients
who have received autologous or allogeneic stem
cell transplantation are not eligible. Administra-
tion of hydroxyurea to control high WBC count prior to, during and after registration is permitted.
Patients must have adequate cardiac function as
defined in the protocol. Patients must be at least
18 years of age, must have a Zubrod performance
status of 0, 1, or 2, and must have adequate renal
and hepatic function. Patients must not have clin-
ical evidence of leptomeningeal disease and must
not have a systemic fungal, bacterial, viral or oth-
er infection that is not controlled. Patients not
known to be HIV+ must be tested for HIV infec-tion. Patients who are HIV+ may be eligible pro-
viding they meet all of the criteria in the protocol.
Accrual Goals The accrual goal of this study is 50 eligible pa-
tients.
Summary Statement As of December 31, 2010, ten patients have been accrued. Two patients were taken off protocol
therapy due to toxicities (infection and decreased
cardiac function) and two were taken off protocol
therapy to pursue transplant.
One of the nine patients evaluated for toxicity
died while on treatment due to hypoxia which is
currently under review for relationship to proto-
col treatment. No other patients have reported
Grade 4 or higher non-hematologic toxicities dur-
ing induction or consolidation therapy.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 44
S0919/II
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg
Cleveland Clinic OH
6
New Mexico MBCCOP 3
Puget Sound 1
Total (3 Institutions) 10
Registration, Eligibility, and Evaluability
Registrations ending December 31, 2010; Data as of February 4, 2011
Pravastatin+
Idarubicin+
Ara-C
Pravastatin+
Idarubicin+
Ara-C
NUMBER REGISTERED
10 ADVERSE EVENT ASSESSMENT
ELIGIBLE 10 Evaluable 9 Too Early 1
Patient Characteristics
Registrations ending December 31, 2010; Data as of February 4, 2011
Pravastatin+Idarubicin+Ara-C Pravastatin+Idarubicin+Ara-C
(n=10) (n=10)
AGE HISPANIC
Median 52.7 Yes 2 20% Minimum 23.2 No 7 70% Maximum 71.3 Unknown 1 10% SEX RACE Males 4 40% White 10 100% Females 6 60%
Treatment Summary
Registrations ending December 31, 2010; Data as of February 4, 2011
Pravastatin+
Idarubicin+
Ara-C
NUMBER ON PROTOCOL TREATMENT
2
NUMBER OFF PROTOCOL TREATMENT 8 REASON OFF TREATMENT Treatment completed as planned 3 Adverse Events or side effects 2 Refusal unrelated to adverse events 0 Progression/relapse 0 Death 1 Other - not protocol specified 2 Reason under review 0MAJOR PROTOCOL DEVIATIONS 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 45
S0919/II
Number of Patients with a Given Type and Grade of Adverse Event
Adverse Events Unlikely or Not Related to Treatment Excluded
Non-Hematologic Adverse Events Only
Adverse Events with No Entries for Grades 3 to 5 Have Been Suppressed
Registrations ending December 31, 2010; Data as of February 4, 2011
Pravastatin+
Idarubicin+Ara-C
Pravastatin+
Idarubicin+Ara-C
(n=9) (n=9)
Grade
Grade
ADVERSE EVENT ≤ 2 3 4 5 ADVERSE EVENT ≤ 2 3 4 5
Cardiac General-other
8 0 1 0
Ocular-other
8 1 0 0
Febrile neutropenia 6 3 0 0 Pulmonary hypertension 8 1 0 0Hypokalemia 6 2 1 0 Pulmonary-other 8 0 0 1Hypophosphatemia 8 1 0 0 Inf, 3-4 ANC: blood 8 1 0 0 MAXIMUM GRADE ANY ADVERSE EVENT Lung Inf, 3-4 ANC: lung 8 1 0 0 Number 4 4 0 1Nausea 8 1 0 0
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 46
C10403/II
C10403 Phase II Intergroup
Coordinating Group: CALGB
An Intergroup Phase II Clinical Trial for Adolescents and Young Adults
with Untreated Acute Lymphoblastic Leukemia (ALL)
Intergroup Participants: CALGB, SWOG, ECOG
Study Coordinators: W Stock (CALGB), A Advani, S Luger (ECOG)
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 1/15/2008
Schema
R E G I S T R A T I
O N
VCR, IV MTX, IT MTX, PEG-Asp
DNR, VCR, Prednisone, PEG-Asp, Ara-C, IT MTX
DOXO, VCR, Dexamethasone, PEG-Asp, IT MTX, CTX, Ara-C, 6TG
Induction Consolidation
CTX, Ara-C, 6-MP, VCR, IT MTX, PEG-Asp
Interim Maintenance
Delayed Intensification
VCR, Dexamethasone, 6-MP, PO MTX, IT MTX
Maintenance
Objectives To describe the outcomes (CR rate, EFS, DFS,
and OS) when adolescents and young adults
(AYA) with newly diagnosed ALL are treated
with a pediatric chemotherapy regimen by adult
hematologists/oncologists at multiple sites. The
feasibility of extending the "pediatric approach" in adults up to age 40 and estimating DFS and OS
also will be explored.
To describe the toxicities observed in these pa-
tients.
To compare the outcomes of the AYA patients
treated on this protocol with appropriate similar
patients (by age and disease characteristics)
treated by pediatric oncologists on Children's On-
cology Group study AALL0232.
To evaluate the adherence of adult hematolo-
gists/oncologists and their patients to a "pedia-
tric" ALL treatment regimen and identify reasons
for variances.
To analyze and describe the outcomes of AYA
patients treated on this study according to pre-
treatment characteristics, such as age, gender,
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 47
C10403/II
white blood cell count, other hematologic para-
meters, blood chemistry, immunophenotype, cy-
togenetics and molecular genetic characteristics,
and treatment variables, such as treatment site
(academic center or community), and protocol
adherence.
To analyze and describe the outcome of AYA pa-
tients treated on this study according to baseline
psychosocial characteristics, demographics, and
family support.
Patient Population Patients must have either B-precursor or T-
precursor acute lymphoblastic leukemia. Patients
with Burkitt type leukemia (FAB L3; SIg posi-tive; t(8;14) or variant, etc.) are not eligible. Pa-
tients known to have Ph+ ALL at the time of di-
agnosis are not eligible.
Patients may have had no prior therapy for acute
leukemia except emergency therapy for blast cell
crisis (corticosteroids or hydroxyurea), superior
vena cava syndrome, or renal failure due to leu-
kemic infiltration of the kidneys. When indicated,
leukapheresis or exchange transfusion are rec-ommended to reduce the WBC. Single-dose intra-
thecal cytarabine is allowed prior to registration
or prior to initiation of systemic therapy for pa-
tient convenience. Systemic chemotherapy must
begin within 72 hours of this intrathecal therapy.
Patients receiving prior steroid therapy are eligi-
ble for this study. The dose and duration of pre-
vious steroid therapy should be carefully docu-
mented.
Adult patients who meet any of the following cri-
teria should be considered for a successor study
for Ph+ ALL: 1) BCR-ABL fusion transcript de-
termined by FISH or RT-PCR or 2)
t(9;22)(q34;q11) or variant determined by cyto-
genetics.
Patients must be between 16 and 40 years of age
and have an ECOG performance status of 0, 1, or
2. Patients with Downs Syndrome are excluded
from this study due to the likelihood of excessive toxicity resulting.
Accrual Goals Up to 300 AYA patients will be enrolled onto this
study.
Summary Statement The study activated in CALGB on November 15,
2007 and at SWOG institutions on January 15, 2008. As of December 31, 2010, 151 patients
have been accrued to this study including 35 from
SWOG institutions.
A complete June 2010 summary of this study
from CALGB is available on the SWOG web
site.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg
Stanford University
15
Cleveland Clinic OH 8MUSC, Hollings CC 3Kentucky, U of 2New Mexico MBCCOP 2Wayne State Univ 2Michigan CRC CCOP 1Michigan, U of 1
Wichita CCOP 1
Total (9 Institutions) 35
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 48
C10404/II
C10404 Phase II Intergroup
Coordinating Group: CALGB
A Genetic Risk-Stratified, Randomized Phase II Study of Four
Fludarabine/Antibody Combinations for Patients with Symptomatic,
Previously Untreated Chronic Lymphocytic Leukemia
Intergroup Participants: CALGB, SWOG, ECOG, NCIC CTG
Study Coordinators: J Byrd (CALGB), J Godwin, S Couban (NCIC CTG),
M Smith (ECOG)
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 3/15/2009
Schema
R
A N D O M I Z E
Arm A: Fludarabine Rituximab (1 cycle)
No further treatment
Induction
Arm B: Fludarabine Rituximab (1 cycle)
Arm C: Fludarabine Rituximab Cyclophosphamide (cycles 1-6)
CR/PR/SD Consolidation:
Lenalidomide
Progression No further treatment
Observe (3 months)
del(11q22.3)
no Arm A: (cycles 2-6)
Observe (3 months)
No further treatment
yes
Arm D: Fludarabine Rituximab Cyclophosphamide
(cycles 2-6)
del(11q22.3)
no Arm B: (cycles 2-6)
yes Arm D:
Fludarabine Rituximab Cyclophosphamide (cycles 2-6)
Observe (3 months)
Observe (3 months)
Observe (3 months)
*(See below)
* Response evaluation
Objectives To determine the two-year progression-free sur-
vival (PFS) after remission induction with four
different chemo-immunotherapy combinations
for patients with untreated, symptomatic, lower
risk and high risk chronic lymphocytic leukemia
(CLL) to decide which of the four arms, if any, to
take forward into a randomized Phase III investi-
gation.
To determine the induction response to FR and
FCR in each of these arms, along with the consol-
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 49
C10404/II
idation response to lenalidomide in patients with
CLL.
To determine the toxicity from these four che-
moimmunotherapy combinations and that of con-solidation therapy with lenalidomide.
To determine the induction response and toxicity
of FCR in patients with del(11q22.3) along with
consolidation response, 2-year PFS and toxicity
of lenalidomide in this specific genetic group.
To determine the effect of pretreatment biologic
characteristics on clinical outcomes, such as at-
taining a complete response to induction therapy and progression-free survival.
To collect relapse samples to determine the fre-
quency of clonal evolution among patients with
IgVH mutated and unmutated disease and to study
mechanisms of resistance to chemoimmunothera-
py.
To determine if flow cytometry negative status
immediately post-therapy at 24 months after study entry is an effective surrogate marker for
prolonged progression-free survival and overall
survival.
Patient Population Patients must have an absolute lymphocytosis of
> 5,000/µL. Morphologically, the lymphocytes
must appear mature with < 55% prolymphocytes.
Bone marrow examination must include at least a
unilateral aspirate and biopsy. The aspirate smear must show > 30% of all nucleated cells to be
lymphoid or the bone marrow core biopsy must
show lymphoid infiltrates compatible with mar-
row involvement by CLL. Overall cellularity
must be normocellular or hypercellular. Local in-
stitution lymphocyte phenotype must reveal a
predominant B-cell monoclonal population shar-
ing a B-cell marker (CD19, CD20, CD23) with
the CD5 antigen, in the absence of other pan-T-
cell markers. Additionally, the B-cells must be
monoclonal with regard to expression of either
kappa or lambda and have surface immunoglobu-lin expression of low density. Patients with bright
surface immunoglobulin levels must have CD23
coexpression. Patients must have symptomatic
and active intermediate or high-risk categories of
the modified three-stage Rai staging system, as
defined in the protocol. Patients in the interme-
diate-risk group must have evidence of active
disease as demonstrated by a least one of the fol-
lowing criteria: massive or progressive spleno-
megaly, hepatomegaly and/or lymphadenopathy;
presence of weight loss > 10% over the preceding
six month period; Grade 2 or 3 fatigue; fevers >
100.5 degrees F or night sweats for greater than
two weeks without evidence of infection; pro-
gressive lymphocytosis with an increase of > 50% over a two month period or an anticipated
doubling time of less than six months.
Patients must have had no prior therapy for CLL,
including no corticosteroids for autoimmune
complications that have developed since the ini-
tial diagnosis of CLL. Patients must not have any
medical condition requiring chronic use of oral
corticosteroids.
Patients must be 18 years of age or older and
must have performance status of 0, 1, or 2. Pa-
tients with HIV infection may be eligible pro-
vided they meet the following criteria: no evi-
dence of infection with hepatitis B or C; CD4+
cell count > 350/mm³; no evidence of resistant
strains of HIV; if not on anti-HIV therapy, an
HIV viral load < 10,000 copies HIV RNA/mL; if
on HIV therapy, HIV viral load < 50 copies HIV
RNA/mL; and no history of AIDS-defining con-
dition. Patients receiving concurrent zidovudine or stavudine may not be enrolled because of over-
lapping protocol toxicities. Patients must have
adequate renal function.
Stratification/Descriptive Factors The randomization will be stratified by Rai stage
at diagnosis: Stage I vs Stage II vs Stage III vs
Stage IV.
Accrual Goals The accrual goal for this study is 405 patients.
Summary Statement The study activated in CALGB on January 15,
2008 and for SWOG institutions on March 15,
2009. On November 2, 2009, the study was rede-
signed to include a reassignment of patients ran-
domized to Arms A and B with the del(11q22.3)
abnormality to receive the Fludara-
bine/Cyclophosphamide/Rituximab remission in-duction therapy for cycles two through six.
As of December 31, 2010, 213 patients have been
accrued to this study, ten from SWOG institu-
tions.
A complete June 2010 summary of this study
from CALGB is available on the SWOG web
site.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 50
C10404/II
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg
MUSC, Hollings CC
4
New Mexico MBCCOP 2Lahey Clinic Med Ctr/Davis, U of CA 1St Louis University 1Thompson Ca Surv Ctr/San Antonio, U of TX 1
Wichita CCOP 1
Total (6 Institutions) 10
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 51
C10603/III
C10603 Phase III SWOG Endorsed CTSU Study
Coordinating Group: CALGB
A Phase III Randomized, Double-Blind Study of Induction
(Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine)
Chemotherapy + Midostaurin (PKC412)(IND #101261) or Placebo in Newly
Diagnosed Patients < 60 Years of Age with FLT3 Mutated Acute Myeloid
Leukemia (AML)
Participants: CALGB, CTSU
Study Coordinators: R Stone (CALGB), B Medeiros (SWOG)
Date Activated: 2/1/2009
Schema
R
E G
I
S
T
R
A
T
I
O
N
Cytarabine +
Daunorubicin + Midostaurin
(1 or 2 cycles)
Cytarabine +
Daunorubicin +
Placebo
(1 or 2 cycles)
Placebo
(12 months)
Consolidation
P
R
E
R
E
G
I
S
T
R
A
T
I
O
N
F
L
T 3
S
C
R
E
E
N
I
N
G
R
A
N D
O
M
I
Z
A
T
I
O
N
Induction
CR
CR
High-dose
Cytarabine + Midostaurin
(4 cycles)
High-dose
Cytarabine +
Placebo
(4 cycles)
Midostaurin (12 months)
Continuation
Objectives To determine if the addition of midostaurin to
daunorubicin/cytarabine induction, high-dose cy-
tarabine consolidation, and continuation therapy
improves overall survival (OS) in both the mutant
FLT3-ITD and FLT3-TKD AML patients.
To compare the overall survival (OS) in the two
groups using an analysis in which patients who
receive a stem cell transplant are censored at the
time of transplant.
To compare the complete response rate between
the two treatment groups.
To compare the event-free survival (EFS) be-
tween the two treatment groups.
To compare the disease-free survival of the two
treatment groups.
To compare the disease-free survival rate one
year after completion of the continuation phase of
the two groups.
To assess the toxicity of the experimental combi-
nation.
To describe the interaction between treatment
outcome and pretreatment characteristics such as
age, performance status, white blood cell (WBC)
count, morphology, cytogenetics, and molecular
and pharmacodynamic features.
To assess the population pharmacokinetics
(popPK) of midostaurin and its two major meta-
bolites, CGP52421 and CGP62221. The potential
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 52
C10603/III
associations between PK exposure, FLT3 status,
OS, EFS, and clinical response will be explored.
Patient Population Patients must have an unequivocal diagnosis of AML (>20% blasts in the bone marrow based on
the WHO classification), excluding M3 (acute
promyelocytic leukemia). AML patients with a
history of antecedent myelodysplasia (MDS) are
eligible for treatment on this trial, but must not
have had prior cytotoxic therapy. Patients must
have documented FLT3 mutation (ITD or point
mutation), determined by analysis in a protocol-
designated FLT3 screening laboratory (see proto-
col Section 6.0).
Patients must not have had prior chemotherapy
for leukemia or myelodysplasia with the follow-
ing exceptions: emergency leukapheresis, emer-
gency treatment for hyperleukocytosis with hy-
droxyurea for ≤ 5 days, cranial RT for CNS leu-
kostasis (one dose only), or growth factor or cy-
tokine support.
Patients who have developed therapy-related
AML after prior RT or chemotherapy for another cancer or disorder are not eligible. Patients must
be at least 18 and less than 60 years old. Patients
must have adequate renal function and must not
have symptomatic congestive heart failure. Pa-
tients with neurologic symptoms suggestive of
CNS leukemia are recommended to have a lum-
bar puncture. Patients whose CSF is positive for
AML blasts are not eligible.
Stratification/Descriptive Factors Treatment randomization will be stratified by
FLT3 mutation status: ITD allelic ratio < 0.7 vs
ITD allelic ratio ≥ 0.7 vs TKD.
Accrual Goals The accrual goal of the study is 514 patients for
the randomization registration.
Summary Statement SWOG has endorsed this study through the Can-
cer Trials Support Unit (CTSU) of the National
Cancer Institute. Please contact the CTSU direct-
ly by either phone (1-888-823-5923) or on the
CTSU web site (http://www.ctsu.org/) for infor-
mation and registration procedures.
The study was activated for CALGB institutions
on April, 1, 2008. As of December 31, 2010, a to-
tal of 553 patients have been randomized to re-ceive treatment on this study, 20 from SWOG in-
stitutions.
A complete November 2010 summary of this
study from CALGB is available on the SWOG
web site.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg Institutions Total
Reg
MUSC, Hollings CC
5 Davis, U of CA
1Stanford University 3 Irvine, U of CA 1H Lee Moffitt CC 2 Loyola University 1Providence Hosp 2 St Joseph's/Candler/H Lee Moffitt CC 1
Atlanta Reg CCOP 1 Wichita CCOP 1
Baylor College 1 Total (12 Institutions) 20Boston Univ Med Ctr 1
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 53
C10701/II
C10701 Phase II SWOG Endorsed CTSU Study
Coordinating Group: CALGB
A Phase II Study of Dasatinib (Sprycel®)(IND #73969, NSC #732517) as
Primary Therapy Followed by Transplantation for Adults ≥ 50 Years with
Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG,
SWOG and NCIC CTG
Participants: CALGB, CTSU
Study Coordinator: M Wetzler (CALGB)
Schema
R E G I S T R A T I O N
Course I Dasatinib (Das) + Dexamethasone (Dex)
Dasatinib maintenance
Allogeneic transplant age 50-70 with matched donor
Course VI
< 20% blasts
Evaluate Marrow
A: CotrimoxazoleDS (Cot) + Das + Dex
> 20% blasts B: Cot + Das + Dex + VCR + DNR
No CR
CR
Course II
Course III
Cot + Das + CTX + VCR + DNR + Dex
CR
CNS prophylaxis: Cot + Das + VCR + MTX + LCV
Course IV
*
*
Course V
Autologous transplant age 50-70 without matched donor
Alternative chemotherapy age >70 or not transplant candidate: VP16 + Ara-C + G-CSF
Objectives Estimate the activity of dasatinib to prolong dis-
ease-free survival (DFS) and overall survival
(OS) in newly diagnosed patients 50 years or old-
er who have Ph+ (BCR/ABL+) ALL.
Determine the activity of dasatinib to prolong
disease-free survival (DFS) and overall survival
(OS) in ALL patients with t(9;22).
Determine the ability of dasatinib to produce or
maintain a BCR/ABL-negative status, as judged
by Q-PCR following sequential dasatinib, chemo-
therapy, and HCT.
Determine the feasibility of collecting adequate
peripheral blood stem cells for autologous HCT
following dasatinib therapy, and assess for resi-dual Ph+ (BCR/ABL+) cells by Q-PCR.
Study the safety and efficacy of autologous HCT
following therapy with dasatinib.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 54
C10701/II
Study the safety and efficacy of reduced-intensity
preparatory regimen followed by an allogeneic
HCT following induction therapy with dasatinib.
Study the safety and efficacy of dasatinib main-tenance administered after allogeneic or autolog-
ous HCT or chemotherapy.
Correlate serum and CSF levels of dasatinib
when given orally during induction.
Validate clinical laboratory results of Q-PCR
measurements in a central laboratory (via
CALGB 9862 for CALGB institutions).
Evaluate the ability of T/NK cell expansion to
predict outcome in patients diagnosed with Ph+
ALL.
Patient Population Patients must have an unequivocal histologic di-
agnosis of ALL and must have the detection of
the t(9;22)(q34;q11) or 3-way variant by meta-
phase cytogenetics or BCR-ABL positive status
by molecular analysis (Q-PCR or FISH) in a CLIA-approved laboratory.
Patients must have no prior therapy except up to
one week of corticosteroids and/or hydroxyurea
to enable time for the detection of
t(9;22)(q34;q11) or BCR/ABL.
Patients must be 50 years of age or older.
Accrual Goals The accrual goal for this study is 60 evaluable pa-
tients.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 55
E1905/II
E1905 Phase II Intergroup
Coordinating Group: ECOG
A Randomized Phase II Trial of Azacitidine With or Without the Histone
Deacetylase Inhibitor Entinostat for the Treatment of Myelodysplastic
Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute
Myeloid Leukemia with Multilineage Dysplasia
Intergroup Participants: ECOG, SWOG, CALGB
Study Coordinators: S Gore (ECOG), H Erba, J Gabrilove (CALGB)
Statisticians: H Gundacker, K Kopecky
Data Coordinator: T Maher
Date Activated: 10/1/2006
Schema
R A N D O M I Z E
CR, PR, HI-major: Continue treatment
Arm A Azacitidine
Evaluate for response
Arm B Azacitidine and Entinostat
HI-minor, no response, progression: Off study treatment
Objectives To estimate the overall response rate (complete,
partial, and hematologic improvement-major by
the International Working Group (IWG) response
criteria) in response to Azacitidine and Entinos-
tat.
To estimate the major response rate (complete and partial responses by the IWG criteria) to a
10-day regimen of Azacitidine and to the same
regimen of Azacitidine in combination with Enti-
nostat administered orally on days 3 and 10 of
each cycle in patients with de novo MDS,
CMMoL (dysplastic type) and AML-TLD, as
well as in patients with treatment-induced MDS,
CMMoL (dysplastic type) and AML-TLD.
To evaluate the toxicity of Azacitidine and Enti-
nostat in this patient population.
To identify changes in gene promoter methylation
and gene expression which may be associated
with response to Azacitidine and Entinostat.
To identify other molecular mechanisms (such as
DNA damage) which may be associated with re-
sponse to Azacitidine and Entinostat.
Patient Population Patients must have one of the following diagnos-
es confirmed by a bone marrow aspirate and/or
biopsy within two weeks prior to registration. 1)
Myelodysplastic Syndrome: Patients with any In-
ternational Prognostic Score (IPSS) are eligible.
Patients with low or INT-1 IPSS must have a
platelet count < 50,000/mm³ and/or absolute neu-
trophil count < 500/mm³ within seven days prior
to registration. 2) Chronic Myelomonocytic Leu-
kemia (Dysplastic subtype): Patients with CMMoL must have a WBC < 12,000/mm³, do-
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 56
E1905/II
cumented within four weeks prior to study entry.
3) AML-TLD will be interpreted to include pa-
tients formally diagnosed by FAB criteria as
RAEB-t, as well as patients with no history of an-
tecedent hematologic disorder who have AML
which meets criteria for AML-TLD by WHO cri-teria. Patients with AML-TLD must have a WBC
≤ 30,000/mm³ documented within four weeks
prior to study entry. Patients whose WBC has
doubled within this period of time and is greater
than 20,000/mm³ at the time of screening will not
be eligible. Patients who have therapy-induced
MDS, CMMoL (dysplastic type), and AML-TLD
are eligible and will be treated as separate cohorts
from the patients with de novo MDS, CMMoL
(dysplastic type) and AML-TLD.
Patients must have no prior treatment with Azaci-
tidine, decitabine, or Entinostat. Patients must not
have received any AML induction chemotherapy
or stem cell transplantation. Patients must not
have received any other treatment for their dis-
ease, including hematopoietic growth factors,
within three weeks prior to registration, and
should have recovered from all toxicities of prior
therapy.
Patients must be at least 18 years of age and an
ECOG performance status of 0, 1, or 2. Women
must not be pregnant or breast-feeding. Patients
must have no active infections at the time of reg-
istration and no clinical evidence of CNS or pul-
monary leukostasis, disseminated intravascular
coagulation, or CNS leukemia. Patients must not
have advanced malignant hepatic tumors and
must not have known hypersensitivity to Azaciti-
dine or mannitol. Patients must have adequate
hepatic and renal function and have no serious or
uncontrolled medical condition. Patients must have a life expectancy of at least six months.
Stratification/Descriptive Factors Patients with secondary disease will accrue to a
separate cohort. At randomization, patients will
be stratified by diagnosis: MDS High/Int-2 vs
MDS Low/Int-1 vs CMMoL vs AML-TLD.
Accrual Goals Non-treatment-induced Cohort:
Initially, 31 eligible patients per arm (62 patients
for both arms) will be accrued. If fewer than six
patients achieve CR, PR, or trilineage response,
accrual to that arm will be closed. Otherwise, 37
additional eligible patients per arm will be ac-
crued for a maximum total of 136 eligible pa-
tients.
Treatment-induced Cohort:
A maximum of 40 treatment-induced eligible pa-
tients will be accrued.
Summary Statement This study opened at ECOG institutions on Au-
gust 18, 2006 and at SWOG institutions on Octo-ber 1, 2006. The study met its first stage accrual
goal and was temporarily closed on September 5,
2007. The study was opened to the second stage
of accrual at ECOG institutions on May 20, 2008
and at SWOG institutions on June 15, 2008.
The study enrolled the planned number of pa-
tients and accrual was closed to the non-
treatment-induced cohort effective May 14, 2009.
The study team prepared an amendment to accrue only to a new cohort of patients with treatment-
related MDS. The amendment was activated at
ECOG institutions on July 22, 2009 and at
SWOG institutions on August 15, 2009.
As of December 31, 2010, 184 patients were reg-
istered including 22 from SWOG institutions.
The complete November 2010 summary of this
study from ECOG is available on the SWOG web site.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg Institutions Total
Reg
Tennessee, U of
4 Michigan, U of
1Montana CCOP 3 Mississippi, Univ of 1Adirondack Ca Care/Rochester, Univ of 2 Ozarks Reg CCOP 1St Louis CCOP 2 Poudre Valley Hosp/Colorado, U of 1Akron Gen Med Ctr/Cleveland Clinic OH 1 Santa Rosa CCOP 1Boston Univ Med Ctr 1 Southeast CCC CCOP 1
Kansas City CCOP 1 Sutter Hlth CRG-East/Davis, U of CA 1
MD Anderson, Florida/Arkansas, U of 1 Total (15 Institutions) 22
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 57
E1908/II
E1908 Phase II SWOG Endorsed CTSU Study
Coordinating Group: ECOG
A Phase II Randomized Trial Comparing Standard and Low Dose
Rituximab: Initial Treatment of Progressive Chronic Lymphocytic
Leukemia in Elderly Patients Using Alemtuzumab and Rituximab
Participants: ECOG, CTSU
Study Coordinators: C Zent (ECOG), E Libby (SWOG)
Date Activated: 11/15/2010
Schema
P R E
R E G I S T R A T I O N
Risk stratification
R A N D O M I Z E
Arm A: Alemtuzumab + standard dose Rituximab (2 or 3 cycles)
CCR
Event monitoring (5 years)
Observation
Arm A or B as randomized previously
PR or stable
Arm B: Alemtuzumab + low dose Rituximab (2 or 3 cycles)
MRD+
Confirm
MRD+
MRD -
Progression
Response evaluation
MRD -
See below
Objectives To compare the rate of complete and overall re-
sponse of patients treated with the two regimens
to determine if the use of modified dose ritux-
imab significantly affects outcome.
To monitor and assess toxicity of these regimens.
To determine the overall and progression-free
survival, time to clinical response, time to next treatment, and duration of response in elderly
CLL patients using these treatment regimens.
To assess the correlation between the risk stratifi-cation prognostic markers (i.e. CD38, ZAP-70,
FISH and IgVH mutation) and clinical outcome.
To assess response to this therapy using both the
NCI-WG96 criteria and an expanded definition of
response for patients in complete remission in-
cluding immunohistochemical examination of the
bone marrow and sensitive flow cytometry (4-6
color) of blood for minimal residual disease
(MRD) and CT scans for residual adenopathy.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 58
E1908/II
To determine the mechanism of action of ritux-
imab and alemtuzumab and to detail the in vivo
effect of the combination of alemtuzumab and ri-
tuximab on critical aspects of the immune system
in CLL from select patients.
Patient Population Patients must have a diagnosis of CLL with min-
imum threshold peripheral lymphocyte count of 5
x 109/L (CLL variant) or palpable adenopathy > 1
cm or palpable splenomegaly (SLL variant) and
immunophenotypic demonstrations of a popula-
tion of B-lymphocytes (as defined by CD19+)
which are monoclonal (by light chain exclusion).
CLL will be diagnosed if these cells have ≥ 3 of
the following characteristics: CD5+, CD23+, dim
surface light chain expression, and dim surface CD20 expression. FISH analysis must be nega-
tive for IGH/CCND1 and/or immunostaining is
negative for cyclin D1 expression to exclude
mantle cell lymphoma. Patients must have pro-
gressive CLL defined as at least one of the fol-
lowing characteristics based on standard criteria
for treatment based on NCI-WG96: weight loss >
10% within the previous six months attributable
to progressive CLL (grade 2 or higher); extreme
fatigue attributable to progressive CLL (grade 3
or higher); fevers > 100.5 degrees F for two weeks without evidence of infection (grade 1 or
higher); night sweats without evidence of infec-
tion (drenching); evidence of progressive bone
marrow failure with hemoglobin < 11 g/dL or
platelet count < 100 x109/L; rapidly progressive
lymphadenopathy providing that the largest node
is not > 5 cm in any dimension.
Patients must not have had any previous treat-
ment for CLL. Patients must not have had con-
comitant use of continuous systemic corticostero-ids.
Patients must be 70 years of age or older and
have an ECOG performance status ≤ 3. Patients
must not have splenomegaly > 6 cm below left
costal margin, at rest, on clinical examination and
not have lymphadenopathy > 5 cm in any diame-
ter. Patients must have adequate renal and hepatic
function. Patients must not have any of the fol-
lowing comorbid conditions: New York Heart
Association Class III or IV heart disease; recent
myocardial infarction (< 1 month prior to regis-tration); uncontrolled infection; infection with the
human immunodeficiency virus (HIV/AIDS); se-
rological evidence of active hepatitis B infection
(HBsAg or HBeAg positive); positive hepatitis C
serology. Patients must not have evidence of ac-
tive autoimmune hemolytic anemia, immune
thrombocytopenia, or pure red blood cell aplasia.
Patients must not have had major surgery within
four weeks prior to pre-registration.
Stratification/Descriptive Factors At randomization, patients will be stratified by
FISH risk classification: 17p13- or 11q22- (high
risk) vs 12+, any other abnormality (without
17p13-, 11q22- or 13q14-), or no abnormality (in-
termediate risk) vs 13q14- as only abnormality
(mono- or biallelic) (low risk).
Accrual Goals Forty patients will be randomized equally to each
of the two treatment arms for a total of 80 eligible patients.
Summary Statement SWOG has endorsed this study through the Can-
cer Trials Support Unit (CTSU) of the National
Cancer Institute. Please contact the CTSU direct-
ly by either phone (1-888-823-5923) or on the
CTSU web site (http://www.ctsu.org/) for infor-
mation and registration procedures.
The study was activated at ECOG on October 8,
2010. SWOG endorsed the study on November
15, 2010. No patients have been accrued as of
December 31, 2010.
The complete November 2010 summary of this
study from ECOG is available on the SWOG web
site.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 59
E2905/III
E2905 Phase III SWOG Endorsed CTSU Study
Coordinating Group: ECOG
Randomized Phase III Trial Comparing the Frequency of Major Erythroid
Response (MER) to Treatment with Lenalidomide (Revlimid®) Alone and in
Combination with Epoetin Alfa (Procrit®) in Subjects with Low- or
Intermediate-1 Risk MDS and Symptomatic Anemia
Participants: ECOG, CTSU
Study Coordinators: A List (ECOG), C Schiffer (SWOG)
Date Activated: 2/15/2009
Schema
Arm B: Lenalidomide and Epoetin Alpha
R A N D O M I Z E
*
MER Continue Arm A treatment until relapse/progression, then offer crossover to Arm B (Step 2)
Offer crossover to Arm B (Step 2) or discontinue study treatment
Continue Arm B treatment until relapse/progression
Discontinue study treatment
Step 1
Arm A: Lenalidomide
no MER
MER
no MER
* Patients with the del 5q31.1 abnormality will not be randomized but will be assigned to Arm A.
Objectives To compare the rate of major erythroid response
(MER) between lenalidomide monotherapy and
combined treatment of lenalidomide and epoetin
alfa in EPO non-responsive Low/Int-1 risk MDS
patients or EPO-treatment naive patients with low
probability of EPO benefit.
To compare the time to MER by treatment as-
signment.
To evaluate the duration of MER by treatment as-
signment.
To estimate the frequency of MER to salvage
combination therapy in patients who fail to expe-
rience a MER with lenalidomide monotherapy.
To evaluate and compare the frequency of minor
erythroid response by treatment assignment.
To investigate the mechanism and target of lena-
lidomide action in patients with chromosome
5q31.1 deletion.
To evaluate the frequency of cytogenetic re-
sponse and progression, and the relation between
cytogenetic pattern and erythroid response.
To evaluate the frequency of bone marrow re-
sponse (CR+PR).
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 60
E2905/III
To evaluate the relationship between erythroid re-
sponse and laboratory correlates of the following:
Pretreatment and onstudy endogenous EPO level
(Arm A); (a) To evaluate the effect of CD45 iso-
form profile on lenalidomide enhancement of
EPO-induced STAT5 phosphorylation in CD71Hi erythroid precursors and the relationship to eryt-
hroid response. (b) To characterize molecular tar-
gets relevant to lenalidomide cytotoxicity in
del5q cells. (c) To evaluate the frequency of cryp-
tic chromosome 5q31 deletions in patients with
non-del5q MDS by array-based genomic scan,
and to determine the relationship to hematologic
response.
Patient Population Patients must have documented diagnosis of MDS lasting at least three months according to
WHO criteria or non-proliferative chronic mye-
lomonocytic leukemia. Patients must have Inter-
national Prognostic Scoring System (IPSS) cate-
gories of Low- or Intermediate-1 risk disease. Pa-
tients must have IPSS score determined by cyto-
genetic analysis prior to randomization. Patients
with cytogenetic failure and < 10% marrow blasts
will be eligible. Patients with cytogenetic failure
must have previous cytogenetic results (FISH is
not a substitute) within the last six months post last type of MDS treatment (in this case, not re-
ferring to growth factors as type of MDS treat-
ment). Patients must have symptomatic anemia
untransfused with hemoglobin ≤ 9.5 g/dL within
eight weeks of registration or with RBC transfu-
sion-dependence (i.e., ≥ 2 units/month) confirmed
for a minimum of eight weeks before randomiza-
tion. Patients must not have proliferative (WBC ≥
12,000/mcL) chronic myelomonocytic leukemia.
Patients must not have MDS secondary to treat-
ment with radiotherapy, chemotherapy, and/or
immunotherapy for malignant or autoimmune diseases.
Patients must have failed treatment with an eryt-
hropoietic growth factor, or have a low probabili-
ty of response to rhu-EPO, as defined in the pro-
tocol, eight weeks prior to randomization. Pa-
tients must be off all non-transfusion therapy for
MDS for 28 days prior to initiation of study
treatment. Patients may receive hydrocortisone
prophylactically to prevent transfusion reactions. Patients must not have prior therapy with lenali-
domide or have used cytotoxic chemotherapeutic
agents, or experimental agents for the treatment
of MDS within eight weeks prior to randomiza-
tion.
Patients must be at least 18 years of age. Patients
must have an EPO level prior to randomization
and ≤ 56 days before day 1 of study treatment.
Patients must not have documented iron deficien-
cy and must have documented marrow iron
stores. If marrow iron stain is not available, the
transferrin saturation must be > 20% or a serum
ferritin > 100 ng/mL. Women must not be preg-
nant or breastfeeding and all females of child-
bearing potential must have two negative preg-nancy tests, the first performed within 14 days
and the second within 24 hours prior to prescrib-
ing lenalidomide. Patients must have the follow-
ing lab values documented on two occasions (se-
parated by at least seven days) over 21 days prior
to randomization: Platelet count ≥ 50,000/mcL
without platelet transfusion, ANC ≥ 500
cells/mcL, serum creatinine ≤ 1.5 x ULN, serum
SGOT or SGPT ≤ 2.0 x ULN, serum total biliru-
bin < 3.0 mg/dL. Patients must not have had prior
≥ Grade 3 allergic reaction to thalidomide, must
not have had a known allergic reaction to epoetin alfa or human serum albumin, and must not have
prior desquamating rash at time of study entry.
Patients must not have anemia resulting from
iron, B12, or folate deficiencies, autoimmune or
hereditary hemolysis, or gastrointestinal bleeding.
Patients must not have a history of thromboem-
bolic events within three years prior to randomi-
zation. Patients must not have known HIV-1 se-
ropositivity, uncontrolled seizure, or uncontrolled
hypertension.
Stratification/Descriptive Factors At randomization patients will be stratified by (1)
serum erythropoietin level: ≤ 500 mU/mL vs >
500 mU/mL, and (2) prior erythropoietic growth
factor treatment: yes vs no. All patients with del
5q31.1 karyotype will be assigned to treatment
with lenalidomide monotherapy (Arm A).
Accrual Goals The study requires 212 patients without 5q31.1 deletion. The estimated accrual goal is a total of
236 eligible patients.
Summary Statement SWOG has endorsed this study through the Can-
cer Trials Support Unit (CTSU) of the National
Cancer Institute. Please contact the CTSU direct-
ly by either phone (1-888-823-5923) or on the
CTSU web site (http://www.ctsu.org/) for infor-
mation and registration procedures.
The study was activated at ECOG on January 29,
2009. SWOG endorsed the study on February 15,
2009. Accrual was suspended on September 23,
2010 due to a recall of epoetin alfa and was reo-
pened on February 4, 2011 when a new supply
became available.
As of December 31, 2010, 67 patients were regis-
tered to this study, twelve from SWOG institu-tions.
APRIL 14 - 16, 2011 SOUTHWEST ONCOLOGY GROUP LEUKEMIA 61
E2905/III
The complete November 2010 summary of this
study from ECOG is available on the SWOG web
site.
Registration by Institution
Registrations ending December 31, 2010
Institutions Total
Reg
H Lee Moffitt CC
5
Davis, U of CA 2Montana CCOP 2Lahey Clinic Med Ctr/Davis, U of CA 1Wayne State Univ 1
Winthrop - Univ Hosp/Columbia University 1
Total (6 Institutions) 12