Clinical trial NCT00987493: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent adult diffuse large cell lymphoma
recurrent grade 3 follicular lymphoma
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2009-10-01
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose-limiting toxicity (phase I)
timeFrame: at 4 weeks.
measure: Maximum-tolerated dose (phase I)
timeFrame: at the end of phase I (31 August 2011)
measure: Objective response (complete and partial response) (phase II)
timeFrame: phase II (3 years)
Secondary outcomes:
measure: Adverse events according to NCI CTCAE v. 3.0
timeFrame: All AEs will be assessed according to NCI CTCAE v3.0 until 30 days after trial therapy end.
measure: Event-free survival (phase II)
timeFrame: up to 30 months for each patient.
measure: Response duration (phase II)
timeFrame: up to 30 months for each patient.
measure: Time to progression (phase II)
timeFrame: up to 30 months for each patient.
measure: Overall survival (phase II)
timeFrame: up to 30 months for each patient.
measure: Quality of life
timeFrame: approx. 5 months for each patient.
measure: Usefulness and feasibility of the SAKK C-SGA
timeFrame: End of phase II (excluding follow-up) at 3 years.
measure: Association between WHO performance status, QOL indicators, and SAKK C-SGA scores
timeFrame: End of phase II (excluding follow-up) at 3 years.
measure: Progression Free Survival (PFS)
timeFrame: up to 30 months for each patient.
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Basel
country: Switzerland
facility: St. Claraspital AG
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Fribourg
country: Switzerland
facility: Hopital Fribourgeois
city: Geneva 14
country: Switzerland
facility: Hôpitaux Universitaires de Genève HUG
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Zürich
country: Switzerland
facility: Universitäts Spital Zürich
Study officials:
affiliation: Cantonal Hospital of St. Gallen
name: Felicitas Hitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kantonsspital Graubünden
name: Mey Ulrich, MD
role: STUDY_CHAIR
References:
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.
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.