Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive B-cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT01582776|
Recruitment Status : Active, not recruiting
First Posted : April 23, 2012
Last Update Posted : August 22, 2018
This study is to determine first the appropriate dose of lenalidomide to administer in combination with fixed doses of obinutuzumab in relapsed/refractory follicular lymphoma patients.
In a second step, this study aims to determine the efficacy of this combination in 3 separate populations: relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4).
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma Patients (Phase IB) Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)||Drug: Lenalidomide and GA101||Phase 1 Phase 2|
This study is an open label, multicenter study with two phases:
The Phase IB part of the study is a dose escalation study of lenalidomide (Revlimid) administered orally during on 3 weeks of every 28-day cycle, in combination with fixed doses of obinutuzumab (GA101) in relapsed/refractory follicular lymphoma patients.
The Phase II part of the study is an efficacy study of the association of the recommended dose of lenalidomide associated with GA101 in 2 separate populations of patients: relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma: cohort 1), relapsed/refractory follicular lymphoma (cohort 2) and previously untreated follicular lymphoma (cohorts 3 and 4). First, all patients will receive a combination of obinutuzumab and lenalidomide for a total of 6 cycles. Patients who achieve at least a partial response after 6 cycles will receive a maintenance treatment with obinutuzumab for 2 years and Lenalidomide for 1 year as tolerated, or until disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||317 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Follicular and Relapsed/Refractory Aggressive (DLBCL and MCL) B-cell Lymphoma|
|Actual Study Start Date :||October 3, 2012|
|Actual Primary Completion Date :||July 11, 2018|
|Estimated Study Completion Date :||March 2022|
Experimental: Lenalidomide and GA101
Ga101 and lenalidomide
Drug: Lenalidomide and GA101
1000mg of GA101 on D8, D15 and D22of cycle 1 and on D1 of cycles 2 to 6. Oral lenalidomide once daily at 10/15/20/25mg (phase I part) or at recommended dose (phase II part) on days 1 to 21 of a 28-day cycle for the first cycle and on days 2 to 22 of a 28-day cycle for cycles 2 to 6.
- Phase I part: Determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 [ Time Frame: 28 days ]The determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 will be performed by a dose escalation approach. Dose Limiting Toxicities (DLTs) observed during the administration of the first 2 cycles of the study will be listed for each escalation step.
- Phase II part: Overall Response Rate (CR+CRu+PR) after 6 cycles [ Time Frame: 24 weeks ]Response rates at the end of treatment including maintenance will be expressed as percentages with their 95% Exact Clopper Pearson Confidence Interval limits
- Overall survival (OS) [ Time Frame: Up to 4.5 years ]
Overall survival will be measured from the date of inclusion to the date of death from any cause.
Alive patients will be censored at their last date known to be alive
- Event Free survival [ Time Frame: Up to 4.5 years ]Event-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause.
- Progression free survival [ Time Frame: Up to 4.5 years ]Progression-Free Survival will be measured according to the Cheson 2007 criteria. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
- Response duration [ Time Frame: Up to 4.5 years ]Patients alive and free of progression will be censored at their last follow-up date
- Response rate at the end of maintenance treatment [ Time Frame: 2.5 years ]Response rates will be evaluated at the end of maintenance phase for patients who achieve a CR/PR after induction treatment and received at least one dose of maintenance. 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, 2007)). Patient without response assessment after maintenance treatment (due to whatever reason) will be considered as non-responder.
- Complete response rate after induction [ Time Frame: 24 weeks ]Disease response evaluation after 6 cycles will be used to determine the Complete Response Rate. Response after 6 cycles will be assessed only if patient completes induction phase. 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 and 2007)).
- Complete response rate after 3 cycles [ Time Frame: 12 weeks ]
Disease response evaluation after 3 cycles will be used to determine the Complete Response Rate.
Response after 3 cycles will be assessed at the end of completion of the 3 cycles if patient received all 3 cycles or at withdrawal. 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 and 2007).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01582776
|Antwerpen, Belgium, 2060|
|A.Z. Sint Jan AV|
|Bruges, Belgium, 8000|
|institut Jules Bordet|
|Bruxelles, Belgium, 1000|
|Université Catholique de Louvain Saint Luc|
|Bruxelles, Belgium, 1200|
|AZ Groeninge - Campus Maria's Voorzienigheid|
|Kortrijk, Belgium, 8500|
|CHU de Liège|
|Liège, Belgium, 4000|
|Université Catholique de Louvain Mont Godinne|
|Yvoir, Belgium, 5530|
|Amiens, France, 80054|
|Bordeaux, France, 33076|
|Institut d'Hématologie de Basse Normandie|
|Caen, France, 14076|
|Clermont-Ferrand, France, 63000|
|Hôpital Henri Mondor|
|Créteil, France, 94010|
|CHU de Dijon|
|Dijon, France, 21034|
|CHU de Grenoble|
|Grenoble, France, 38043|
|CHRU de Lille|
|Lille, France, 59037|
|Centre Léon Bérard|
|Lyon, France, 69373|
|Institut Paoli Calmette|
|Marseille, France, 13273|
|CHU St Eloi|
|Montpellier, France, 34295|
|Nancy, France, 54511|
|CHU Hôtel Dieu|
|Nantes, France, 44093|
|Hôpital St Louis|
|Paris, France, 75475|
|Centre François Magendie|
|Pessac, France, 33604|
|CH Lyon Sud|
|Pierre Bénite, France, 69495|
|Rennes, France, 35003|
|Centre henri Becquerel|
|Rouen, France, 76038|
|Principal Investigator:||Franck MORSCHHAUSER, Professor||Lymphoma Study Association|
|Principal Investigator:||Roch HOUOT, Professor||Lymphoma Study Association|