The Combination of Rad001 and Rituximab In Patients With Non-hodgkin's Lymphomas ((RAD001-R))
This study is an open label, multicenter study with two phases:
- Phase I is a dose escalation study of RAD001 in combination with one injection of Rituximab 375 mg/m² per week during 4 weeks (28 days) in patients CD20 positive non-Hodgkin's lymphomas to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD). The purpose of the study is to assess the feasibility of the combination based on - rate of dose limiting toxicities (DLT) and PK drug-drug interaction (DDI).
- Phase II will define the efficacy and safety profile of RAD001 and Rituximab combination at the RP2D in patients with lymphomas.
Patients with lymphomas will be treated at the RP2D established during phase I and evaluated for clinical benefit rate, comprising complete responses (CR + CRu), partial responses (PR) and stable disease (SD), and time to progression using the IWG criteria for treatment response.
Induction therapy will follow the same schedule than during the phase I study.
Maintenance therapy: Monthly cycles for up to 2 years with:
- Daily RAD001 at the same dose than during induction therapy.
- Rituximab infusion every other cycle at 375 mg/m2 that correspond to the usual maintenance schedule for Rituximab.
Response to therapy will be assessed between day 42 and day 49, then every two months.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study Investigating the Combination of RAD001 and Rituximab in Patients With Non-Hodgkin's Lymphomas|
- Phase I part: Determination of the Recommended Dose of RAD001 in combination with rituximab. [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Determination of recommended dose will be based on safety parameters and particularly on incidence of DLTs .
- Phase II part: Complete Response Rate (CR+CRu) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma Cheson,1999)
- OVERALL RESPONSE RATE [ Time Frame: 2 years ] [ Designated as safety issue: No ]The same disease response assessment used for complete response rate will be considered to determine the Overall Response Rate. Patient is defined as a responder if he/she has a complete response (CR/CRu) or partial response (PR) at the end of treatment. A descriptive analysis will also be performed considering as nonresponders all patients who relapsed or died during treatment phase even if they were prematurely withdrawn as responder.
- PROGRESSION-FREE SURVIVAL [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Progression-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
- OVERALL SURVIVAL [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Overall survival will be measured from the date of inclusion to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of the last contact.
- DURATION OF RESPONSE [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Duration of response will be measured from the date of first documentation of a response (CR/CRu or PR after induction or at the end of treatment) to the date of first documented evidence of progression/relapse or death from any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
|Experimental: Everolimus and rituximab||
Drug: Everolimus and rituximab
One injection of Rituximab 375 mg/m2 per week during 28 days followed by one Rituximab infusion every other cycle at 375 mg/m2 associated with everolimus at 5mg or 10 mg every day or 5 mg every other day.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01567475
|Service des Maladies du Sang - CHRU de Lille|
|Lille, France, 59037|
|Service Hématologie - Hôtel Dieu de NANTES|
|Nantes, France, 44035|
|Service Hématologie - CHU Lyon Sud|
|Pierre-Bénite, France, 69495|
|Service Hématologie - Centre Henri Becquerel|
|Rouen, France, 76038|
|Service Hématologie - Institut Gustave Roussy|
|Villejuif, France, 94805|
|Principal Investigator:||Vincent RIBRAG, Doctor||Service Hématologie, Institut Gustave Roussy|