Clinical trial NCT00864942: Trial of Bendamustine, Lenalidomide and Rituximab in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)
Official title: Phase I Clinical Trial of Bendamustine, Lenalidomide and Rituximab in B-Cell Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia
Non-Hodgkin's Lymphoma
Keywords: CLL
NHL
lymphoma
Lead sponsor: Georgetown University
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Cephalon
First posted: 2009-03-19
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is for subjects with a B-cell lymphoid malignancy (lymphoma) or chronic lymphocytic leukemia (CLL) that has come back after or did not get better with previous treatment. The purpose of this study is to find out the highest dose of lenalidomide that can be given together with bendamustine and rituximab. The study will also look what effects the combination of lenalidomide and bendamustine and the combination of lenalidomide, bendamustine and rituximab will have on patients and their disease.

Detailed description: This is a Phase I, open-label, dose-escalation study of bendamustine and lenalidomide (BL) and also bendamustine,lenalidomide, and rituximab (BLR) in relapsed/refractory CLL and relapsed/refractory B-cell lymphomas. Phase I dose escalation will be done independently for the CLL and NHL groups. In addition, the study will be conducted in 2 parts. In part I of the study, the maximum tolerated dose of bendamustine and lenalidomide will be determined independently for the CLL and NHL groups. In part II of the study, CLL and NHL subjects will be enrolled at the MTD of BL determined in Part I for CLL and NHL and all subjects will receive rituximab. Part II of the study will determine the MTD of BLT independently for the NHL and CLL groups.

Eligibility criteria: Inclusion Criteria:

* Documented relapsed or refractory B-cell NHL; CD-20 positive tumor. Indolent NHL: follicular B-cell lymphoma, diffuse small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, transformed aggressive lymphomas, mantle cell lymphoma and chronic lymphocytic leukemia
* Maximum of 6 prior chemotherapy regimens. Prior rituximab is allowed.
* Bidimensionally measurable disease
* ECOG performance status 0-2
* Absolute neutrophil count \>/= 1000 and platelet count \>/= 50,000
* Serum creatinine \</= 1.5 mg/dL
* Adequate hepatic function
* Estimated life expectancy of at least 3 months
* All study participants must be registered into the mandatory RevAssist program and be willing and able to comply with the requirements of RevAssist
* Able to take aspirin 81 mg daily as prophylactic anticoagulation

Exclusion Criteria:

* Chemotherapy or immunotherapy within 3 weeks prior to entering study or failure to recover from adverse events due to any agents administered previously
* Use of investigational agents within 28 days of study
* Hematopoietic growth factors within 14 days of study
* History of prior high dose chemotherapy with allogeneic stem cell support
* History of prior radioimmunotherapy \</= 1 year
* Concurrent treatment with therapeutic doses of systemic steroids
* Pregnant or lactating female subjects
* Concurrent, active malignancy other than lymphoma or CLL
* Primary CNS lymphoma
* Patients with a prior diagnosis of lymphoma active in the CNS are eligible only if CNS has been treated, and they are neurologically stable with no progressive symptoms off steroids and anti-convulsants
* Serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, might interfere with the achievement of study objectives
* Hypersensitivity to murine proteins or to any component of rituximab
* Known positive for HIV or infectious hepatitis type C; hepatitis type B that is active and uncontrolled
* Hypersensitivity to mannitol
* Evidence of laboratory tumor lysis syndrome by Cairo-Bishop criteria
* Subject with recent thromboembolic event (deep vein thrombosis or pulmonary embolism) unless clinically stable and event occurred more than 2 weeks prior to enrollment.

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 2 years
measure: Dose limiting toxicity
timeFrame: 2 years
measure: Recommended Phase II dose
timeFrame: 2 years
Secondary outcomes:
measure: overall safety profile
timeFrame: 2 years
measure: Plasma pharmacokinetics
timeFrame: 2 years
measure: Preliminary antitumor activity
timeFrame: 2 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital/Lombardi Cancer Center
state: District of Columbia
Study officials:
affiliation: Georgetown University
name: Bruce D Cheson, MD
role: PRINCIPAL_INVESTIGATOR
References: