Rituximab, Bendamustine Hydrochloride, and Lenalidomide in Treating Patients With Aggressive B-Cell Lymphoma
This study is currently recruiting participants.
Verified November 2012 by Swiss Group for Clinical Cancer Research
Sponsor:
Swiss Group for Clinical Cancer Research
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00987493
First received: September 30, 2009
Last updated: November 26, 2012
Last verified: November 2012
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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
| Estimated 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:
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00987493
Contacts
| Contact: Katrin Eckhardt, PhD | +41 31 389 92 31 | Katrin.Eckhardt@sakk.ch |
Locations
| Switzerland | |
| Kantonsspital Baden | Recruiting |
| Baden, Switzerland, CH-5404 | |
| Contact: Clemens B. Caspar, MD 41-56-486-2511 clemens.caspar@ksb.ch | |
| Principal Investigator: Clemens B. Caspar, MD | |
| St. Claraspital AG | Recruiting |
| Basel, Switzerland, CH-4016 | |
| Contact: Christian Ludwig, Prof. 41-61-691-8585 christian.ludwig@claraspital.ch | |
| Principal Investigator: Christian Ludwig, Prof. | |
| Universitaetsspital Basel | Recruiting |
| Basel, Switzerland, 4031 | |
| Contact: Fatime Krasniqi, MD +41 61 265 5059 KrasniqiF@uhbs.ch | |
| Principal Investigator: Fatime Krasniqi, MD | |
| Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli | Recruiting |
| Bellinzona, Switzerland, 6500 | |
| Contact: Emanuele Zucca, MD 41-91-811-6772 ielsg@ticino.com | |
| Principal Investigator: Emanuele Zucca, MD | |
| Inselspital Bern | Recruiting |
| Bern, Switzerland, 3010 | |
| Contact: Thomas Pabst, Prof. +41 31 632 84 30 thomas.pabst@insel.ch | |
| Principal Investigator: Thomas Pabst, Prof | |
| Kantonsspital Bruderholz | Recruiting |
| Bruderholz, Switzerland, CH-4101 | |
| Contact: Lorenz M. Jost, MD 41-61-436-3636 lorenz.jost@ksbh.ch | |
| Principal Investigator: Lorenz M. Jost, MD | |
| Kantonsspital Graubünden | Recruiting |
| Chur, Switzerland, 7000 | |
| Contact: Ulrich Mey, PD +41 81 256 71 70 ulrich.mey@ksgr.ch | |
| Principal Investigator: Ulrich Mey, MD | |
| Hopital Fribourgeois | Recruiting |
| Fribourg, Switzerland, 1708 | |
| Contact: Daniel Betticher, MD 41-26-426-7240 betticherd@h-fr.ch | |
| Principal Investigator: Daniel Betticher, MD | |
| Hôpitaux Universitaires de Genève HUG | Recruiting |
| Geneva 14, Switzerland, 1211 | |
| Contact: Haroun Khalafallah, MD +41 22 372 29 07 haroun.khalfallah@hcuge.ch | |
| Principal Investigator: Haroun Khalafallah, MD | |
| Centre Hospitalier Universitaire Vaudois | Recruiting |
| Lausanne, Switzerland, CH-1011 | |
| Contact: Grégoire Berthod, MD +41 21 314 01 55 Gregoire.berthod@chuv.ch | |
| Principal Investigator: Grégoire Berthod, MD | |
| Kantonsspital Liestal | Recruiting |
| Liestal, Switzerland, CH-4410 | |
| Contact: Andreas Lohri, MD 41-61-925-2710 andreas.lohri@ksli.ch | |
| Principal Investigator: Andreas Lohri, MD | |
| Kantonsspital Olten | Recruiting |
| Olten, Switzerland, CH-4600 | |
| Contact: Walter Mingrone, MD 41-62-311-4241 wmingrone_ol@spital.ktso.ch | |
| Principal Investigator: Walter Mingrone, MD | |
| Kantonsspital St. Gallen | Recruiting |
| St. Gallen, Switzerland, 9007 | |
| Contact: Felicitas Hitz, MD +41 71 494 10 66 felicitas.hitz@kssg.ch | |
| Principal Investigator: Felicitas Hitz, MD | |
| Kantonsspital Winterthur | Recruiting |
| Winterthur, Switzerland, 8401 | |
| Contact: Natalie Fischer, MD +41 052 266 40 87 natalie.fischer@ksw.ch | |
| Principal Investigator: Natalie Fischer, MD | |
| Universitäts Spital Zürich | Recruiting |
| Zürich, Switzerland, 8091 | |
| Contact: Christoph Renner, Prof. +41 44 255 89 02 christoph.renner@usz.ch | |
| Principal Investigator: Christoph Renner, Prof | |
| Stadtspital Triemli | Recruiting |
| Zürich, Switzerland, 8063 | |
| Contact: Reto Kühne, MD +41 44 466 12 71 reto.kuehne@triemli.stzh.ch | |
| Principal Investigator: Reto Kühne, MD | |
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
| Principal Investigator: | Felicitas Hitz, MD | Kantonsspital 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: | November 26, 2012 |
| 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 Rituximab Lenalidomide Nitrogen Mustard Compounds Thalidomide Antineoplastic Agents |
Therapeutic Uses Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Immunosuppressive Agents Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances |
ClinicalTrials.gov processed this record on May 22, 2013