Trial of Bendamustine, Lenalidomide and Rituximab in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL)

Chronic Lymphocytic Leukemia Clinical Trial

— Phase I BLR  

Official title:

Phase I Clinical Trial of Bendamustine, Lenalidomide and Rituximab in B-Cell Lymphoid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00864942
• Other study ID #: RV-CLL-NHL-PI-356
• Secondary ID: 2008-186
• Status: Completed
• Phase: Phase 1
• First received: March 17, 2009
• Last updated: March 12, 2015
• Start date: February 2009
• Est. completion date: October 2014

Study information

• Verified date: June 2014
• Source: Georgetown University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• bendamustine and lenalidomide
Lenalidomide is given daily orally for one week followed by bendamustine HCL 90 mg/m2 IV over 30 to 60 minutes on days 1 and 2 in combination with lenalidomide, given orally, in dose-escalating cohorts. After a maximum of 6 cycles of combination therapy with bendamustine and lenalidomide, lenalidomide monotherapy is continued for an additional 6 cycles as tolerated or until disease progression.
• BL-NHL
Bendamustine HCL 90 mg/m2 given intravenously over 30 to 60 minutes on days 1 and 2 in combination with lenalidomide, given orally, in dose-escalating cohorts. After a maximum of 6 cycles of combination therapy with bendamustine and lenalidomide, lenalidomide monotherapy is continued for an additional 6 cycles as tolerated or until disease progression.
• BLR-CLL
Lenalidomide is given orally for 7 days followed by rituximab 375 mg/m2 on day 1 in addition to bendamustine 90 mg/m2 intravenously over 30-60 minutes on days 1 and 2 and lenalidomide orally daily every 28 days for a total of 6 cycles. After 6 cycles of bendamustine, lenalidomide and rituximab, lenalidomide monotherapy is administered as continued therapy for an additional 6 cycles as tolerated or until disease progression.
• BLR-NHL
Rituximab 375 mg/m2 is given on day 1 on day 1 in addition to bendamustine 90 mg/m2 intravenously over 30-60 minutes on days 1 and 2 and lenalidomide orally daily every 28 days for a total of 6 cycles. After 6 cycles of bendamustine, lenalidomide and rituximab, lenalidomide monotherapy is administered as continued therapy for an additional 6 cycles as tolerated or until disease progression.

Locations

Country	Name	City	State
United States	Georgetown University Hospital/Lombardi Cancer Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Georgetown University	Celgene Corporation, Cephalon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose		2 years	Yes
Primary	Dose limiting toxicity		2 years	Yes
Primary	Recommended Phase II dose		2 years	Yes
Secondary	overall safety profile		2 years	Yes
Secondary	Plasma pharmacokinetics		2 years	No
Secondary	Preliminary antitumor activity		2 years	No