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

May 14, 2019 updated by: Swiss Group for Clinical Cancer Research

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Baden, Switzerland, CH-5404
        • Kantonsspital Baden
      • Basel, Switzerland, CH-4016
        • St. Claraspital AG
      • Basel, Switzerland, 4031
        • Universitaetsspital Basel
      • Bellinzona, Switzerland, 6500
        • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
      • Bern, Switzerland, 3010
        • Inselspital Bern
      • Bruderholz, Switzerland, CH-4101
        • Kantonsspital Bruderholz
      • Chur, Switzerland, 7000
        • Kantonsspital Graubünden
      • Fribourg, Switzerland, 1708
        • Hôpital Fribourgeois
      • Geneva 14, Switzerland, 1211
        • Hôpitaux Universitaires de Genève HUG
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • Liestal, Switzerland, CH-4410
        • Kantonsspital Liestal
      • Olten, Switzerland, CH-4600
        • Kantonsspital Olten
      • St. Gallen, Switzerland, 9007
        • Kantonsspital St. Gallen
      • Winterthur, Switzerland, 8401
        • Kantonsspital Winterthur
      • Zürich, Switzerland, 8063
        • Stadtspital Triemli
      • Zürich, Switzerland, 8091
        • Universitäts Spital Zürich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
All AEs will be assessed according to NCI CTCAE v3.0 until 30 days after trial therapy end.
Event-free survival (phase II)
Time Frame: up to 30 months for each patient.
up to 30 months for each patient.
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
up to 30 months for each patient.
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
up to 30 months for each patient.
Overall survival (phase II)
Time Frame: up to 30 months for each patient.
up to 30 months for each patient.
Quality of life
Time Frame: approx. 5 months for each patient.
approx. 5 months for each patient.
Usefulness and feasibility of the SAKK C-SGA
Time Frame: End of phase II (excluding follow-up) at 3 years.
End of phase II (excluding follow-up) at 3 years.
Association between WHO performance status, QOL indicators, and SAKK C-SGA scores
Time Frame: End of phase II (excluding follow-up) at 3 years.
End of phase II (excluding follow-up) at 3 years.
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
up to 30 months for each patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Swiss Group for Clinical Cancer Research

Investigators

  • Principal Investigator: Felicitas Hitz, MD, Cantonal Hospital of St. Gallen
  • Study Chair: Mey Ulrich, MD, Kantonsspital Graubünden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

September 30, 2009

First Submitted That Met QC Criteria

September 30, 2009

First Posted (Estimate)

October 1, 2009

Study Record Updates

Last Update Posted (Actual)

May 15, 2019

Last Update Submitted That Met QC Criteria

May 14, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 38/08
  • SWS-SAKK-38/08
  • 2009-012559-67 (EudraCT Number)
  • EU-20976
  • CDR0000652127

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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