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.
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.
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.
OBJECTIVES:
Primary
Secondary
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.
DISEASE CHARACTERISTICS:
Histologically confirmed aggressive B-cell non-Hodgkin lymphoma, including any of the following:
Meets 1 of the following criteria:
Measurable disease defined as ≥ 1 lesion ≥ 2 cm in greatest transverse diameter on cross-sectional imaging
Must complete pre-treatment cancer-specific geriatric assessment and/or quality-of-life questionnaire (phase II only)
No known CNS involvement
PATIENT CHARACTERISTICS:
WHO performance status (PS) 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT ≤ 2 times ULN
Alkaline phosphatase 2 times ULN
Creatinine clearance > 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 12 months after completion of study therapy
EF ≥ 40% by echocardiography or MUGA scan
Negative HIV test
Able to comply with and geographic proximity to allow proper staging and study follow-up
Agree to follow the special prescribing requirements for lenalidomide
No other malignancy within the past 3 years except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
No unstable cardiovascular disease
No psychiatric disorder precluding understanding of information on trial-related topics, giving informed consent, or interfering with compliance for oral drug intake
No serious underlying medical condition that, in the judgement of the investigator, could impair the ability of the patient to participate in the trial including, but not limited to, any of the following conditions:
No known hypersensitivity to any component of the trial drugs
PRIOR CONCURRENT THERAPY:
Bellinzona, 6500, Switzerland