Lenalidomide Plus Bendamustine and Rituximab for Untreated CLL/SLL

Study Overview
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Brief Summary
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Lenalidomide belongs to a group of drugs called immunomodulatory drugs (IMiD) that can modify or regulate the functioning of the immune system. It is an FDA approved drug for people with multiple myeloma. It is not currently approved for use in Chronic Lymphocytic Leukemia (CLL), but it does appear effective in CLL when used alone, and is being studied for use in combination with chemotherapy in this and other lymphomas and leukemias. In this research study we are hoping to learn more about the effects of lenalidomide on CLL when given in combination with bendamustine and rituximab, which is a highly effective regimen for initial therapy of CLL/SLL. The investigators will be looking for the highest dose of lenalidomide that can be given safely, without causing any serious or unmanageable side effects.

Detailed Description
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Subjects will receive lenalidomide, bendamustine and rituximab in cycles of 28 days (4 weeks). Lenalidomide will be administered orally once daily on days 8-21 of cycle 1 and on days 1-21 of all subsequent cycles. Bendamustine will be administered through a vein (IV infusion) on days 1 and 2 of each cycle. Rituximab will be administered as an IV infusion on day 1 of each cycle. Subjects will receive routine blood tests and physical exam during each cycle. Tumor assessments by CT scan will be performed during cycles 2, 4, and 6.

Official Title
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Lenalidomide in Combination With Bendamustine and Rituximab for Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma(CLL/SLL): a Phase I Study

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, B Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Lenalidomide
* Drug: Bendamustine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with B-cell CLL or SLL (chronic lymphocytic leukemia or small lymphocytic leukemia) Life expectancy > 3 months Organ and marrow function with protocol parameters Able to take aspirin daily Exclusion Criteria: Age >80 years Prior systemic therapy for CLL/SLL including chemotherapy or antibody therapy Pregnant or breast-feeding Serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing informed consent Known hypersensitivity to thalidomide or lenalidomide Prior use of lenalidomide Concurrent use of other anti-cancer agents or treatments HIV positive Prior history of another malignancy unless disease free for at least 2 years Uncontrolled intercurrent illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Lenalidomide|Lenalidomide will be dose escalated until the maximum tolerated dose is reached. The starting dose is 2.5mg, followed by 5mg, followed by 10mg.|
|Drug: Bendamustine|90 mg/m^2 IV days 1-2 of each cycle for 6 cycles|
|Drug: Rituximab|375 mg/m^2 IV day 1 (cycle 1), 500 mg/m^2 day 1 (cycles 2-6)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify the maximum tolerated dose of lenalidomide when combined with bendamustine and rituximab in CLL/SLL |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define dose limiting toxicities of bendamustine, rituximab and lenalidomide in CLL |  | 2 year | 
| Clinical efficacy | response rate, progression-free and overall survival | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, Leukemia, Untreated, B-CLL, SLL