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

NCT00987493 | Completed Phase 1

• 5 other identifiers: SAKK 38/08SWS-SAKK-38/082009-012559-67EU-20976CDR0000652127
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 16

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.

Conditions

Lymphoma

Keywords

recurrent adult diffuse large cell lymphoma; recurrent grade 3 follicular lymphoma

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (phase I)

  at 4 weeks.

• Maximum-tolerated dose (phase I)

  at the end of phase I (31 August 2011)

• Objective response (complete and partial response) (phase II)

  phase II (3 years)

Secondary Outcomes (9)

• Adverse events according to NCI CTCAE v. 3.0

  All AEs will be assessed according to NCI CTCAE v3.0 until 30 days after trial therapy end.

• Event-free survival (phase II)

  up to 30 months for each patient.

• Response duration (phase II)

  up to 30 months for each patient.

• Time to progression (phase II)

  up to 30 months for each patient.

• Overall survival (phase II)

  up to 30 months for each patient.

Study Arms (1)

Treatment with rituximab, bendamustine and lenalidomide

EXPERIMENTAL

Biological: rituximab; Drug: bendamustine hydrochloride; Drug: lenalidomide

Interventions

rituximab BIOLOGICAL

day 1 at a fixed dose of 375mg/m2

Also known as: MabThera, Rituxan

Treatment with rituximab, bendamustine and lenalidomide

bendamustine hydrochloride DRUG

Bendamustine at day 1 and 2 according to the dose escalation in phase I, and at the recommended dose in phase II: 70mg/m2.

Also known as: Cephalon

Treatment with rituximab, bendamustine and lenalidomide

lenalidomide DRUG

Lenalidomide at days 1-21 according to the dose escalation in phase I, and at the recommended dose in phase II: 10mg

Also known as: Revlimid

Treatment with rituximab, bendamustine and lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (16)

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

St. Claraspital AG

Basel, CH-4016, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, CH-4101, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Hopital Fribourgeois

Fribourg, 1708, Switzerland

Location

Hôpitaux Universitaires de Genève HUG

Geneva, 1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Kantonsspital Liestal

Liestal, CH-4410, Switzerland

Location

Kantonsspital Olten

Olten, CH-4600, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

Universitäts Spital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 27018242 RESULT

• 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.

  PMID: 23592273 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

Rituximab; Bendamustine Hydrochloride; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles

Study Officials

• Felicitas Hitz, MD

  Cantonal Hospital of St. Gallen

  PRINCIPAL INVESTIGATOR

• Mey Ulrich, MD

  Kantonsspital Graubünden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: September 1, 2009
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2016
• Last Updated: May 15, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (16)