Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Aggressive B-Cell Lymphoma
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stop the growth of cancer by blocking blood flow to the tumor. Giving rituximab together with bendamustine hydrochloride and lenalidomide may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving rituximab together with bendamustine hydrochloride and lenalidomide in treating patients with aggressive B-cell lymphoma.
Drug: bendamustine hydrochloride
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Rituximab, Bendamustine and Lenalidomide in Patients With Aggressive B-cell Lymphoma Not Eligible for High Dose Chemotherapy or Anthracycline-Based Therapy. A Phase I/II Trial.|
- Dose-limiting toxicity (phase I) [ Time Frame: at 4 weeks. ] [ Designated as safety issue: Yes ]
- Maximum-tolerated dose (phase I) [ Time Frame: at the end of phase I (31 August 2011) ] [ Designated as safety issue: Yes ]
- Objective response (complete and partial response) (phase II) [ Time Frame: phase II (3 years) ] [ Designated as safety issue: No ]
- Adverse events according to NCI CTCAE v. 3.0 [ Time Frame: All AEs will be assessed according to NCI CTCAE v3.0 until 30 days after trial therapy end. ] [ Designated as safety issue: Yes ]
- Event-free survival (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
- Response duration (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]From the time when criteria for response (CR/CRu or PR) are met, until documentation of relapse or progression thereafter. Only patients with a response (CR/ CRu or PR) shall be included in this analysis. Patients with no disease progression or relapse shall be censored at the last time they were known to be in remission
- Time to progression (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]Defined as the time from registration until documented lymphoma progression or death as a result of lymphoma. Patients not experiencing an event will be censored at the last time they were known to be in remission
- Overall survival (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: approx. 5 months for each patient. ] [ Designated as safety issue: No ]
- Usefulness and feasibility of the SAKK C-SGA [ Time Frame: End of phase II (excluding follow-up) at 3 years. ] [ Designated as safety issue: No ]
- Association between WHO performance status, QOL indicators, and SAKK C-SGA scores [ Time Frame: End of phase II (excluding follow-up) at 3 years. ] [ Designated as safety issue: No ]
- Progression Free Survival (PFS) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
Time from registration until one of the following events (whichever occurs first):
- Relapse or progression assessed according to the International Workshop NHL criteria (1999)
- Death of any cause
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||September 2016|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
|Experimental: Treatment with rituximab, bendamustine and lenalidomide||
day 1 at a fixed dose of 375mg/m2
Other Names:Drug: bendamustine hydrochloride
Bendamustine at day 1 and 2 according to the dose escalation in phase I, and at the recommended dose in phase II: 70mg/m2.
Other Name: CephalonDrug: lenalidomide
Lenalidomide at days 1-21 according to the dose escalation in phase I, and at the recommended dose in phase II: 10mg
Other Name: Revlimid
- To determine the maximum-tolerated dose of the combination of rituximab, bendamustine hydrochloride, and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based first-line treatment or intensive regimens including high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in refractory or relapsing disease, or as treatment for patients relapsing after HDT with ASCT. (phase I).
- To identify the recommended dose of this regimen for a phase II study (phase I).
- To determine the efficacy and safety of this regimen in these patients (phase II).
- To assess the quality of life (QOL) of patients treated with this regimen (phase II).
- To evaluate the usefulness and feasibility of the SAKK Cancer-Specific Geriatric Assessment (C-SGA) in patients treated with this regimen (phase II).
- To assess the association between WHO performance status, QOL indicators, and SAKK C-SGA scores (phase II).
- To describe changes in SAKK C-SGA scores from pre- to post-treatment and in QOL (phase II).
OUTLINE: This is a multicenter, phase I dose-escalation study of bendamustine hydrochloride and lenalidomide followed by a phase II study.
Patients receive rituximab IV on day 1, bendamustine hydrochloride IV over 30-60 minutes on days 1-2, and oral lenalidomide on days 1-21. Courses repeat every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients on phase II study complete the SAKK Cancer-Specific Geriatric Assessment at baseline and after completion of course 1. Patients also complete quality-of-life questionnaires at baseline and periodically during study.
After completion of study therapy, patients are followed for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987493
|Baden, Switzerland, CH-5404|
|St. Claraspital AG|
|Basel, Switzerland, CH-4016|
|Basel, Switzerland, 4031|
|Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli|
|Bellinzona, Switzerland, 6500|
|Bern, Switzerland, 3010|
|Bruderholz, Switzerland, CH-4101|
|Chur, Switzerland, 7000|
|Fribourg, Switzerland, 1708|
|Hôpitaux Universitaires de Genève HUG|
|Geneva 14, Switzerland, 1211|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Liestal, Switzerland, CH-4410|
|Olten, Switzerland, CH-4600|
|Kantonsspital St. Gallen|
|St. Gallen, Switzerland, 9007|
|Winterthur, Switzerland, 8401|
|Zürich, Switzerland, 8063|
|Universitäts Spital Zürich|
|Zürich, Switzerland, 8091|
|Principal Investigator:||Felicitas Hitz, MD||Cantonal Hospital of St. Gallen|
|Study Chair:||Mey Ulrich, MD||Kantonsspital Graubünden|