PRIMAInvestigator Meeting

Friday, June 16, 2006Friday, June 16, 2006Grand Sofitel DemeureGrand Sofitel Demeure, Amsterdam, Amsterdam

Stéphanie Baulu, Delphine Germain & Stéphanie Baulu, Delphine Germain & Gilles SallesGilles Salles

AgendaAgenda

Status of the studyStatus of the study Regulatory issuesRegulatory issues Flow of CRFs and queriesFlow of CRFs and queries Flow of SAEsFlow of SAEs Medical questionsMedical questions Financial aspectsFinancial aspects Other questions ?Other questions ?

STATUSSTATUS

2525 countries in Prima Study countries in Prima Study

2323 active countries (at least 1 patient) active countries (at least 1 patient)

740740 patients registered (13/06/06) patients registered (13/06/06)270270 patients randomized (13/06/06) patients randomized (13/06/06)

PRIMA RECRUITMENTPRIMA RECRUITMENTGlobal World Recruitment - PRIMA Study

1 10 2039

6078

108136

174211

257

307

356

429

491

579

638

707740

0

50

100

150

200

250

300

350

400

450

500

550

600

650

700

750

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850

900

Date

Incl

uded

Pat

ient

s

Real Recruitment

Estimated World Recruitment

PRIMA RECRUITMENTPRIMA RECRUITMENT

Country Recruitment - PRIMA study

0

50

100

150

200

250

300

350

400

Country

Nu

mb

er o

f In

clu

ded

Pat

ien

ts

Patients RegisteredPatients Randomized

PRIMA RECRUITMENTPRIMA RECRUITMENT

Chemo regimen chosen

R-CHOP 547 73%R-CVP 167 22%R-FCM 31 4%

Recent increase in R-CVP treated patients

Regulatory AspectsRegulatory Aspects

To be provided to GELARC :To be provided to GELARC : CV of Principal Investigator in each centerCV of Principal Investigator in each center Approvals (Ethics Committee and Health Authorities) Approvals (Ethics Committee and Health Authorities)

for amendment n°2 + regulatory certification documentfor amendment n°2 + regulatory certification document

Insurance extension (OK for all countries)Insurance extension (OK for all countries) After reception of approvals, PI of each center After reception of approvals, PI of each center

will sign an Amendment formwill sign an Amendment form

CRFs FLOW CHARTCRFs FLOW CHART Baseline part (p1 to 9)Baseline part (p1 to 9) => sent to GELARC before => sent to GELARC before

randomizationrandomization Induction / randomization parts (p10 to 18)Induction / randomization parts (p10 to 18) => sent as soon => sent as soon

as possible as possible Maintenance partMaintenance part => every 4 visits (with evaluation and => every 4 visits (with evaluation and

toxicity pages)toxicity pages) Progression, events, deathsProgression, events, deaths : as soon as possible : as soon as possible AE and original forms of SAEAE and original forms of SAE => sent after each => sent after each

monitoring visitmonitoring visit

Remember that all parts have to be monitored Remember that all parts have to be monitored before sending them to GELARCbefore sending them to GELARC

QUERY & DATA MANAGEMENTQUERY & DATA MANAGEMENT

CRFs validationCRFs validation parametered tests + medical reviewparametered tests + medical review

CRFs are validated as followCRFs are validated as follow : : Baseline + induction treatmentBaseline + induction treatment Maintenance (every 4 visits)Maintenance (every 4 visits) Follow-up / progression / death / AEs (at Follow-up / progression / death / AEs (at

reception)reception)

Clinical data correction Forms will be sent by Clinical data correction Forms will be sent by GELARC after the validation of each partGELARC after the validation of each part

QUERY & DATA MANAGEMENTQUERY & DATA MANAGEMENT Clinical data correction Forms will be sent by e-Clinical data correction Forms will be sent by e-

mail to the local coordinator (study group, Roche mail to the local coordinator (study group, Roche or other)or other)

Answers must be completed directly on the form Answers must be completed directly on the form by the investigator (by the investigator (do not forget to sign and do not forget to sign and date form ! date form ! ) )

One copy must be kept in the CRFOne copy must be kept in the CRF Each completed form has to be faxed to Each completed form has to be faxed to

GELARC (ASAP) and original forms have to be GELARC (ASAP) and original forms have to be sent after the next monitoring visit (with CRF sent after the next monitoring visit (with CRF pages)pages)

Clinical data correction formClinical data correction formIdentification of Patient and center

Name and signature of investigator

Your answerQuestion

Proposal for answerActual Data

reported on CRF

CRF Page (s)

Item concerned by query

Serious Adverse EventsSerious Adverse Events

172 SAEs recorded172 SAEs recorded

Record medical diagnosis and not a list of Record medical diagnosis and not a list of symptomssymptoms

Do not forget to send follow-up if necessaryDo not forget to send follow-up if necessary

Queries on SAE are sent directly to the Queries on SAE are sent directly to the center by fax => answer in the same way center by fax => answer in the same way (write answer on the Query form)(write answer on the Query form)

Some clinical aspectsSome clinical aspects“inclusion criteria” (1)“inclusion criteria” (1)

Please note than those have to be fulfilledPlease note than those have to be fulfilled Remember:Remember:

Diagnosis on LYMPH NODE biopsyDiagnosis on LYMPH NODE biopsy Steroids during the last 4 weeks Steroids during the last 4 weeks << 20 mg/day 20 mg/day

equivalentsequivalents Stage I/II should have a high tumor burdenStage I/II should have a high tumor burden Spleen is always > 7 cm and is not a bulk criteria by Spleen is always > 7 cm and is not a bulk criteria by

itself !!itself !! Issues with hepatitis (HIV)Issues with hepatitis (HIV)

Don’t hesitate to ask… gilles.salles@chu-lyon.frDon’t hesitate to ask… gilles.salles@chu-lyon.fr

Some clinical aspectsSome clinical aspects“randomization” (1)“randomization” (1)

Inclusion criteria should be met !Inclusion criteria should be met ! The inclusion data should be sent to GELA-RCThe inclusion data should be sent to GELA-RC

Treatment has to follow the initial protocol Treatment has to follow the initial protocol schemes : doses and schedules schemes : doses and schedules

Only CR and PR patients randomizedOnly CR and PR patients randomized

Why are they only 14 days day tolerated ?Why are they only 14 days day tolerated ?

Some clinical aspectsSome clinical aspects“maintenance or observation”“maintenance or observation”

11) Please follow the protocol recommendations ) Please follow the protocol recommendations forfor

- visits every 8 weeks- visits every 8 weeks- CT scans every 6 months- CT scans every 6 months

2) Please indicate any event/progression as 2) Please indicate any event/progression as soon as it occurssoon as it occurs

The future of PRIMAThe future of PRIMA

- With more than 730 pts recruited, PRIMA is With more than 730 pts recruited, PRIMA is already the largest trial ever performed in first line already the largest trial ever performed in first line follicular lymphoma patientsfollicular lymphoma patients

- Rhythm of inclusion extremely high allowed to Rhythm of inclusion extremely high allowed to extend the population from 640 to 900 pts (675 extend the population from 640 to 900 pts (675 pts randomized)pts randomized)

- An opportunity for answering a very important An opportunity for answering a very important question with a high standard quality trial : question with a high standard quality trial : - Rituximab maintenance benefit after R-chemoRituximab maintenance benefit after R-chemo

Thanks to all of youThanks to all of you

for your cooperationfor your cooperation