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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00987493
First received: September 30, 2009
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Lymphoma
Biological: rituximab
Drug: bendamustine hydrochloride
Drug: lenalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Dose-limiting toxicity (phase I) [ Time Frame: at 4 weeks. ] [ Designated as safety issue: Yes ]
  • Maximum-tolerated dose (phase I) [ Time Frame: at the end of phase I (31 August 2011) ] [ Designated as safety issue: Yes ]
  • Objective response (complete and partial response) (phase II) [ Time Frame: phase II (3 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
  • Event-free survival (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
  • Response duration (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
    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

  • Time to progression (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
    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

  • Overall survival (phase II) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: approx. 5 months for each patient. ] [ Designated as safety issue: No ]
  • Usefulness and feasibility of the SAKK C-SGA [ Time Frame: End of phase II (excluding follow-up) at 3 years. ] [ Designated as safety issue: No ]
  • Association between WHO performance status, QOL indicators, and SAKK C-SGA scores [ Time Frame: End of phase II (excluding follow-up) at 3 years. ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: up to 30 months for each patient. ] [ Designated as safety issue: No ]

    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


Enrollment: 49
Study Start Date: September 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987493

Locations
Switzerland
Kantonsspital Baden
Baden, Switzerland, CH-5404
St. Claraspital AG
Basel, Switzerland, CH-4016
Universitaetsspital Basel
Basel, Switzerland, 4031
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
Universitäts Spital Zürich
Zürich, Switzerland, 8091
Stadtspital Triemli
Zürich, Switzerland, 8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Principal Investigator: Felicitas Hitz, MD Cantonal Hospital of St. Gallen
Study Chair: Mey Ulrich, MD Kantonsspital Graubünden
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00987493     History of Changes
Other Study ID Numbers: SAKK 38/08, SWS-SAKK-38/08, EUDRACT-2009-012559-67, EU-20976, CDR0000652127
Study First Received: September 30, 2009
Last Updated: February 7, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
recurrent adult diffuse large cell lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bendamustine
Nitrogen Mustard Compounds
Rituximab
Lenalidomide
Thalidomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on August 21, 2014