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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
rituximab
bendamustine hydrochloride
lenalidomide
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult diffuse large cell lymphoma, recurrent grade 3 follicular lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kantonsspital Baden
  • Universitaetsspital Basel
  • St. Claraspital AG
  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
  • Inselspital Bern
  • Kantonsspital Bruderholz
  • Kantonsspital Graubünden
  • Hopital Fribourgeois
  • Hôpitaux Universitaires de Genève HUG
  • Centre Hospitalier Universitaire Vaudois
  • Kantonsspital Liestal
  • Kantonsspital Olten
  • Kantonsspital St. Gallen
  • Kantonsspital Winterthur
  • Stadtspital Triemli
  • Universitäts Spital Zürich

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment with rituximab, bendamustine and lenalidomide

Arm Description

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (phase I)
Maximum-tolerated dose (phase I)
Objective response (complete and partial response) (phase II)

Secondary Outcome Measures

Adverse events according to NCI CTCAE v. 3.0
Event-free survival (phase II)
Response duration (phase II)
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)
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)
Quality of life
Usefulness and feasibility of the SAKK C-SGA
Association between WHO performance status, QOL indicators, and SAKK C-SGA scores
Progression Free Survival (PFS)
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

Full Information

First Posted
September 30, 2009
Last Updated
May 14, 2019
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT00987493
Brief Title
Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Aggressive B-Cell Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult diffuse large cell lymphoma, recurrent grade 3 follicular lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment with rituximab, bendamustine and lenalidomide
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
MabThera, Rituxan
Intervention Description
day 1 at a fixed dose of 375mg/m2
Intervention Type
Drug
Intervention Name(s)
bendamustine hydrochloride
Other Intervention Name(s)
Cephalon
Intervention Description
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
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide at days 1-21 according to the dose escalation in phase I, and at the recommended dose in phase II: 10mg
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (phase I)
Time Frame
at 4 weeks.
Title
Maximum-tolerated dose (phase I)
Time Frame
at the end of phase I (31 August 2011)
Title
Objective response (complete and partial response) (phase II)
Time Frame
phase II (3 years)
Secondary Outcome Measure Information:
Title
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.
Title
Event-free survival (phase II)
Time Frame
up to 30 months for each patient.
Title
Response duration (phase II)
Description
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 Frame
up to 30 months for each patient.
Title
Time to progression (phase II)
Description
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
Time Frame
up to 30 months for each patient.
Title
Overall survival (phase II)
Time Frame
up to 30 months for each patient.
Title
Quality of life
Time Frame
approx. 5 months for each patient.
Title
Usefulness and feasibility of the SAKK C-SGA
Time Frame
End of phase II (excluding follow-up) at 3 years.
Title
Association between WHO performance status, QOL indicators, and SAKK C-SGA scores
Time Frame
End of phase II (excluding follow-up) at 3 years.
Title
Progression Free Survival (PFS)
Description
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
Time Frame
up to 30 months for each patient.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felicitas Hitz, MD
Organizational Affiliation
Cantonal Hospital of St. Gallen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mey Ulrich, MD
Organizational Affiliation
Kantonsspital Graubünden
Official's Role
Study Chair
Facility Information:
Facility Name
Kantonsspital Baden
City
Baden
ZIP/Postal Code
CH-5404
Country
Switzerland
Facility Name
Universitaetsspital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
St. Claraspital AG
City
Basel
ZIP/Postal Code
CH-4016
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Kantonsspital Bruderholz
City
Bruderholz
ZIP/Postal Code
CH-4101
Country
Switzerland
Facility Name
Kantonsspital Graubünden
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
Hopital Fribourgeois
City
Fribourg
ZIP/Postal Code
1708
Country
Switzerland
Facility Name
Hôpitaux Universitaires de Genève HUG
City
Geneva 14
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Kantonsspital Liestal
City
Liestal
ZIP/Postal Code
CH-4410
Country
Switzerland
Facility Name
Kantonsspital Olten
City
Olten
ZIP/Postal Code
CH-4600
Country
Switzerland
Facility Name
Kantonsspital St. Gallen
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
8401
Country
Switzerland
Facility Name
Stadtspital Triemli
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
Facility Name
Universitäts Spital Zürich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27018242
Citation
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.
Results Reference
result
PubMed Identifier
23592273
Citation
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.
Results Reference
result

Learn more about this trial

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

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