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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00987493
Recruitment Status : Completed
First Posted : October 1, 2009
Last Update Posted : May 15, 2019
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: bendamustine hydrochloride Drug: lenalidomide Phase 1 Phase 2

Detailed Description:



  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Intervention Model: Single Group Assignment
Masking: None (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.
Study Start Date : September 2009
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2016

Arm Intervention/treatment
Experimental: Treatment with rituximab, bendamustine and lenalidomide Biological: rituximab
day 1 at a fixed dose of 375mg/m2
Other Names:
  • MabThera
  • Rituxan

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: Cephalon

Drug: 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

Primary Outcome Measures :
  1. Dose-limiting toxicity (phase I) [ Time Frame: at 4 weeks. ]
  2. Maximum-tolerated dose (phase I) [ Time Frame: at the end of phase I (31 August 2011) ]
  3. Objective response (complete and partial response) (phase II) [ Time Frame: phase II (3 years) ]

Secondary Outcome Measures :
  1. 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. ]
  2. Event-free survival (phase II) [ Time Frame: up to 30 months for each patient. ]
  3. Response duration (phase II) [ Time Frame: up to 30 months for each patient. ]
    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

  4. Time to progression (phase II) [ Time Frame: up to 30 months for each patient. ]
    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

  5. Overall survival (phase II) [ Time Frame: up to 30 months for each patient. ]
  6. Quality of life [ Time Frame: approx. 5 months for each patient. ]
  7. Usefulness and feasibility of the SAKK C-SGA [ Time Frame: End of phase II (excluding follow-up) at 3 years. ]
  8. Association between WHO performance status, QOL indicators, and SAKK C-SGA scores [ Time Frame: End of phase II (excluding follow-up) at 3 years. ]
  9. Progression Free Survival (PFS) [ Time Frame: up to 30 months for each patient. ]

    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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00987493

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Kantonsspital Baden
Baden, Switzerland, CH-5404
Universitaetsspital Basel
Basel, Switzerland, 4031
St. Claraspital AG
Basel, Switzerland, CH-4016
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, 3010
Kantonsspital Bruderholz
Bruderholz, Switzerland, CH-4101
Kantonsspital Graubünden
Chur, Switzerland, 7000
Hopital Fribourgeois
Fribourg, Switzerland, 1708
Hôpitaux Universitaires de Genève HUG
Geneva 14, Switzerland, 1211
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital Liestal
Liestal, Switzerland, CH-4410
Kantonsspital Olten
Olten, Switzerland, CH-4600
Kantonsspital St. Gallen
St. Gallen, Switzerland, 9007
Kantonsspital Winterthur
Winterthur, Switzerland, 8401
Stadtspital Triemli
Zürich, Switzerland, 8063
Universitäts Spital Zürich
Zürich, Switzerland, 8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
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Principal Investigator: Felicitas Hitz, MD Cantonal Hospital of St. Gallen
Study Chair: Mey Ulrich, MD Kantonsspital Graubünden

Publications of Results:
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Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT00987493     History of Changes
Other Study ID Numbers: SAKK 38/08
2009-012559-67 ( EudraCT Number )
First Posted: October 1, 2009    Key Record Dates
Last Update Posted: May 15, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Swiss Group for Clinical Cancer Research:
recurrent adult diffuse large cell lymphoma
recurrent grade 3 follicular lymphoma
Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bendamustine Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action