Study of Bendamustine/Rituxan Induction Chemotherapy With Revlimid Maintenance for Relapsed/Refractory CLL and SLL

Study Overview
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Brief Summary
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The purpose of this research is to evaluate a new combination of chemotherapy drugs for CLL/SLL using the drugs bendamustine (an intravenous chemotherapy drug), rituximab (an intravenous medication called a monoclonal antibody), and lenalidomide (an anti-cancer pill). The purpose of this study is to see if giving the chemotherapy pill lenalidomide after treatment with bendamustine and rituximab is able to prolong the period of time before the cancer starts growing again and causing symptoms.

Official Title
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Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy With Maintenance Lenalidomide and Rituximab in Relapsed/Refractory CLL/SLL

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed,CLL/SLL, documented relapsed or refractory disease after at least one prior chemotherapy regimen. In cases of SLL, patients must have at least one bidimensionally measurable lesion at least ≥1.5 cm measured in one dimension. ECOG performance status of 0-2 at study entry Laboratory test results within these ranges: ANC <=1500/μL, Platelet count <= 100,000/μL. Patients with ANC <1500/μL or plt <100,000/μL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible. creatinine clearance of >60 mL/min as determined by the Cockcroft-Gault calculation. Total bilirubin <= 2X upper limit laboratory normal (ULN). Patients with non-clinically significant elevations of bilirubin due to Gilbert's disease are not required to meet these criteria. Serum transaminases AST (SGOT) and ALT (SGPT) <=5x ULN, Serum alkaline phosphatase ≤5 X ULN. Disease free of prior malignancies for ≥ 2 years with the exception of basal or squamous cell skin carcinoma, carcinoma in situ of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery). Patients may have received prior therapy with bendamustine or lenalidomide, but must not have disease that is refractory to bendamustine or lenalidomide. Prior therapy with rituximab is permitted, even in the setting of rituximab refractory disease. Exclusion Criteria: Has received >5 lines of prior therapy for their disease. Re-treatment with an identical regimen does not count as a new regimen. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form or comply with the protocol treatment. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking lenalidomide. Prior history or current evidence of central nervous system or leptomeningeal involvement. Use of any other experimental drug or therapy within 28 days of baseline. Known hypersensitivity to thalidomide. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. Known to be positive for HIV or infectious hepatitis, type B or C.

Ages Eligible for Study
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Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Induction/Maintenance chemotherapy<br>Bendamustine + rituximab induction therapy followed by lenalidomide maintenance therapy | Drug: Bendamustine<br>* 90 mg/m2/day IV days 1 and 2 every 28 days for 6 cycles<br>* Other names: Treanda;Drug: Rituximab<br>* 375 mg/m2 Day 1 every 28 days for 6 cycles<br>* Other names: rituxan;Drug: Lenalidomide<br>* 5 mg/day days 1-28 of each 28 day cycle, up to 12 cycles maximum. Dose escalation to 10 mg/day allowed after one cycle as defined in the protocol.<br>* Other names: CC-5013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The primary endpoint of this study was progression-free survival (PFS), defined as the number of days from the day of first study drug administration to the day the patient experienced disease progression or death from any cause. Response and progression in cases of small lymphocytic lymphoma(SLL) were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of chronic lymphocytic leukemia (CLL) were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). | 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up) | 
| Progression-free Survival | Progression-free survival (PFS) is defined as the time from the day of first study drug administration until progression of CLL/SLL or death from any cause. PFS is reported as the proportion of participants with PFS up to 42 months. | 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (Complete + Partial Responses) | Response and progression in cases of SLL were evaluated using the International Working Group Criteria for response in NHL (Cheson, et al 1996). Response and progression in cases of CLL were evaluated using the NCI-sponsored CLL Working Group guidelines for CLL (Cheson, et al 2007). Complete response defined as resolution enlarged lymph nodes, spleen and liver; normalization of blood counts (neutrophils, hemoglobin, platelets); no residual CLL/SLL detectable in the bone marrow. Partial response defined as 50% or more reduction in size of enlarged lymph nodes, liver or spleen; 50% or more improvement of blood counts; 50% or more improvement in the blood lymphocyte count. Progressive disease defined as 50% or more increase in the combined measurements of at least 2 lymph nodes as measured on CT scans or the appearance of new enlarged lymph nodes; 50% of more increase in the size of the spleen or liver; 50% or more increase in blood lymphocyte count. | 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up) | 
| Toxicities Observed With Induction Chemotherapy and Maintenance Therapy | Toxicities were reported using the Common Terminology Criteria for Adverse Events, version 3.0. | 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up) | 
| Overall Survival | Overall survival (OS) is defined as the time from the day of first study drug administration until death from any cause. | 42 months (6 months induction therapy, 12 months maintenance, 24 months long-term follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, SLL