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

Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987493
• Other study ID #: SAKK 38/08
• Secondary ID: SWS-SAKK-38/0820
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2009
• Est. completion date: April 2016

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: April 2016
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• rituximab
day 1 at a fixed dose of 375mg/m2

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

Locations

Country	Name	City	State
Switzerland	Kantonsspital Baden	Baden
Switzerland	St. Claraspital AG	Basel
Switzerland	Universitaetsspital Basel	Basel
Switzerland	Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Bruderholz	Bruderholz
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Hopital Fribourgeois	Fribourg
Switzerland	Hôpitaux Universitaires de Genève HUG	Geneva 14
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital Liestal	Liestal
Switzerland	Kantonsspital Olten	Olten
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Stadtspital Triemli	Zürich
Switzerland	Universitäts Spital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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 eli — View 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 lymphom — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (phase I)		at 4 weeks.
Primary	Maximum-tolerated dose (phase I)		at the end of phase I (31 August 2011)
Primary	Objective response (complete and partial response) (phase II)		phase II (3 years)
Secondary	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.
Secondary	Event-free survival (phase II)		up to 30 months for each patient.
Secondary	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	up to 30 months for each patient.
Secondary	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	up to 30 months for each patient.
Secondary	Overall survival (phase II)		up to 30 months for each patient.
Secondary	Quality of life		approx. 5 months for each patient.
Secondary	Usefulness and feasibility of the SAKK C-SGA		End of phase II (excluding follow-up) at 3 years.
Secondary	Association between WHO performance status, QOL indicators, and SAKK C-SGA scores		End of phase II (excluding follow-up) at 3 years.
Secondary	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	up to 30 months for each patient.