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

Swiss Group for Clinical Cancer Research

Status and phase

Completed

Phase 2

Phase 1

Conditions

Lymphoma

Treatments

Biological: rituximab

Drug: lenalidomide

Drug: bendamustine hydrochloride

Study type

Interventional

Funder types

Other

Identifiers

NCT00987493

SAKK 38/08

CDR0000652127

EU-20976

SWS-SAKK-38/08

2009-012559-67 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

49 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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