PRIMA Investigator Meeting Friday, June 16, 2006 Grand Sofitel Demeure, Amsterdam Stéphanie Baulu, Delphine Germain & Gilles Salles

Agenda Status of the study Status of the study Regulatory issues Regulatory issues Flow of CRFs and queries Flow of CRFs and queries Flow of SAEs Flow of SAEs Medical questions Medical questions Financial aspects Financial aspects Other questions ? Other questions ?

STATUS 25 countries in Prima Study 25 countries in Prima Study 23 active countries (at least 1 patient) 23 active countries (at least 1 patient) 740 patients registered (13/06/06) 740 patients registered (13/06/06) 270 patients randomized (13/06/06) 270 patients randomized (13/06/06)

PRIMA RECRUITMENT

Chemo regimen chosen R-CHOP54773% R-CVP16722% R-FCM 31 4% Recent increase in R-CVP treated patients

Regulatory Aspects To be provided to GELARC : To be provided to GELARC :  CV of Principal Investigator in each center  Approvals (Ethics Committee and Health Authorities) for 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 will sign an Amendment form After reception of approvals, PI of each center will sign an Amendment form

CRFs FLOW CHART Baseline part (p1 to 9) => sent to GELARC before randomization Baseline part (p1 to 9) => sent to GELARC before randomization Induction / randomization parts (p10 to 18) => sent as soon as possible Induction / randomization parts (p10 to 18) => sent as soon as possible Maintenance part => every 4 visits (with evaluation and toxicity pages) Maintenance part => every 4 visits (with evaluation and toxicity pages) Progression, events, deaths : as soon as possible Progression, events, deaths : as soon as possible AE and original forms of SAE => sent after each monitoring visit AE and original forms of SAE => sent after each monitoring visit Remember that all parts have to be monitored before sending them to GELARC

QUERY & DATA MANAGEMENT CRFs validation CRFs validation  parametered tests + medical review CRFs are validated as follow : CRFs are validated as follow :  Baseline + induction treatment  Maintenance (every 4 visits)  Follow-up / progression / death / AEs (at reception) Clinical data correction Forms will be sent by GELARC after the validation of each part Clinical data correction Forms will be sent by GELARC after the validation of each part

QUERY & DATA MANAGEMENT Clinical data correction Forms will be sent by e- mail to the local coordinator (study group, Roche or other) Clinical data correction Forms will be sent by e- mail to the local coordinator (study group, Roche or other) Answers must be completed directly on the form by the investigator (do not forget to sign and date form ! ) Answers must be completed directly on the form by the investigator (do not forget to sign and date form ! ) One copy must be kept in the CRF One copy must be kept in the CRF Each completed form has to be faxed to GELARC (ASAP) and original forms have to be sent after the next monitoring visit (with CRF pages) Each completed form has to be faxed to GELARC (ASAP) and original forms have to be sent after the next monitoring visit (with CRF pages)

Clinical data correction form Identification of Patient and center Name and signature of investigator Your answerQuestion Proposal for answer Actual Data reported on CRF CRF Page (s) Item concerned by query

Serious Adverse Events 172 SAEs recorded 172 SAEs recorded Record medical diagnosis and not a list of symptoms Record medical diagnosis and not a list of symptoms Do not forget to send follow-up if necessary Do not forget to send follow-up if necessary Queries on SAE are sent directly to the center by fax => answer in the same way (write answer on the Query form) Queries on SAE are sent directly to the center by fax => answer in the same way (write answer on the Query form)

Some clinical aspects “inclusion criteria” (1) Please note than those have to be fulfilled Please note than those have to be fulfilled Remember: Remember: Diagnosis on LYMPH NODE biopsy Diagnosis on LYMPH NODE biopsy Steroids during the last 4 weeks < 20 mg/day equivalents Steroids during the last 4 weeks < 20 mg/day equivalents Stage I/II should have a high tumor burden Stage I/II should have a high tumor burden Spleen is always > 7 cm and is not a bulk criteria by itself !! Spleen is always > 7 cm and is not a bulk criteria by itself !! Issues with hepatitis (HIV) Issues with hepatitis (HIV) Don’t hesitate to ask… Don’t hesitate to ask…

Some clinical aspects “randomization” (1) Inclusion criteria should be met ! Inclusion criteria should be met ! The inclusion data should be sent to GELA-RC The inclusion data should be sent to GELA-RC Treatment has to follow the initial protocol schemes : doses and schedules Treatment has to follow the initial protocol schemes : doses and schedules Only CR and PR patients randomized Only CR and PR patients randomized Why are they only 14 days day tolerated ? Why are they only 14 days day tolerated ?

Some clinical aspects “maintenance or observation” 1 ) Please follow the protocol recommendations for - visits every 8 weeks - CT scans every 6 months 2) Please indicate any event/progression as soon as it occurs

The future of PRIMA - With more than 730 pts recruited, PRIMA is already the largest trial ever performed in first line follicular lymphoma patients - Rhythm of inclusion extremely high allowed to extend the population from 640 to 900 pts (675 pts randomized) - An opportunity for answering a very important question with a high standard quality trial : - Rituximab maintenance benefit after R-chemo

Thanks to all of you for your cooperation for your cooperation