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

NCT ID: NCT00987493

Last Updated: 2019-05-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2016-04-30

Brief Summary

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.

Detailed 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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment with rituximab, bendamustine and lenalidomide

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

day 1 at a fixed dose of 375mg/m2

bendamustine hydrochloride

Intervention Type: DRUG

Bendamustine at day 1 and 2 according to the dose escalation in phase I, and at the recommended dose in phase II: 70mg/m2.

lenalidomide

Intervention Type: DRUG

Lenalidomide at days 1-21 according to the dose escalation in phase I, and at the recommended dose in phase II: 10mg

Interventions

rituximab

day 1 at a fixed dose of 375mg/m2

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

lenalidomide

Lenalidomide at days 1-21 according to the dose escalation in phase I, and at the recommended dose in phase II: 10mg

Intervention Type: DRUG

Other Intervention Names

MabThera; Rituxan; Cephalon; Revlimid

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Felicitas Hitz, MD

Role: PRINCIPAL_INVESTIGATOR

Cantonal Hospital of St. Gallen

Mey Ulrich, MD

Role: STUDY_CHAIR

Kantonsspital Graubünden

Locations

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital Basel

Basel, , Switzerland

St. Claraspital AG

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubünden

Chur, , Switzerland

Hopital Fribourgeois

Fribourg, , Switzerland

Hôpitaux Universitaires de Genève HUG

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Stadtspital Triemli

Zurich, , Switzerland

Universitäts Spital Zürich

Zurich, , Switzerland

Countries

Switzerland

References

Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. doi: 10.1111/bjh.14049. Epub 2016 Mar 28.

Reference Type: RESULT

PMID: 27018242 (View on PubMed)

Hitz F, Fischer N, Pabst T, Caspar C, Berthod G, Eckhardt K, Berardi Vilei S, Zucca E, Mey U; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland. Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial. Ann Hematol. 2013 Aug;92(8):1033-40. doi: 10.1007/s00277-013-1751-z. Epub 2013 Apr 17.

Reference Type: RESULT

PMID: 23592273 (View on PubMed)

Other Identifiers

SWS-SAKK-38/08

Identifier Type: -

Identifier Source: secondary_id

2009-012559-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EU-20976

Identifier Type: -

Identifier Source: secondary_id

CDR0000652127

Identifier Type: -

Identifier Source: secondary_id

SAKK 38/08

Identifier Type: -

Identifier Source: org_study_id