Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Aggressive B-Cell Lymphoma

OBJECTIVES:

Primary

• 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).

Secondary

• 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.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive B-cell non-Hodgkin lymphoma, including any of the following:

• Diffuse large B-cell lymphoma (variants, subgroups, and subtypes according to WHO criteria)
• Transformed follicular lymphoma
• Follicular lymphoma grade 3B
• Meets 1 of the following criteria:

• Not eligible for anthracycline-based first-line chemotherapy (e.g., R-CHOP)
• Refractory disease after at least 2 courses of anthracycline-based immune-chemotherapy (e.g., R-CHOP) and patient is not eligible for intensive salvage regimens including HDT with ASCT
• Relapsed disease after at least 1 treatment with curative intention and patient is not eligible for intensive salvage regimens including HDT with ASCT
• Relapsed disease after HDT with ASCT
• 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

• Diagnostic procedures required only in case of specific symptoms

PATIENT CHARACTERISTICS:

• WHO performance status (PS) 0-2

• WHO PS 3 allowed in case of lymphoma-related impaired general condition (phase II only)
• 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:

• Acute or ongoing infection
• Uncontrolled diabetes mellitus
• Active autoimmune disease
• No known hypersensitivity to any component of the trial drugs

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No experimental drugs within the past 30 days
• No concurrent drugs contraindicated with the trial drugs according to the Swissmedic-approved product information
• No other concurrent anticancer or investigational drugs or radiotherapy