Lenalidomide With or Without Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as lenalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining lenalidomide with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying the how well giving lenalidomide with or without rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Determine the best cytostatic response rate (including complete response, partial response, or stable disease) in patients with relapsed or refractory chronic lymphocytic leukemia treated with lenalidomide (CC-5013). Secondary Determine the cytostatic response rate in patients who progress on CC-5013 and are then treated with CC-5013 and rituximab. Determine the safety of these regimens in these patients. Determine time to progression in patients treated with these regimens. OUTLINE: This is an open-label, non-randomized, pilot study. Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR. Patients with disease progression receive oral CC-5013 once daily on days 1-21 and rituximab IV on days 1, 8, and 15 during the first treatment course and on days 1 and 15 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of further disease progression. Patients who achieve CR receive 2 additional courses beyond CR. Patients are followed at 1 month and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 1.5 years.

Official Title
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CC-5013 Alone or in Combination With Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Conditions
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Leukemia

Intervention / Treatment
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* Biological: rituximab
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of chronic lymphocytic leukemia (CLL) by flow cytometry Relapsed or refractory disease Measurable disease, defined by 1 of the following criteria: Absolute lymphocyte count ≥ 5,000/mm^3 Measurable lymphadenopathy or organomegaly Received ≥ 1 prior therapy for CLL PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 30,000/mm^3 Hepatic Bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present) Renal Creatinine ≤ 1.5 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation No known hypersensitivity to thalidomide No erythema nodosum characterized by a desquamating rash after prior thalidomide or similar drug administration No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins No serious medical condition or laboratory abnormality that would preclude study participation No psychiatric illness that would preclude giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy No prior lenalidomide (CC-5013) No concurrent thalidomide Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy No concurrent radiotherapy Surgery Not specified Other At least 4 weeks since prior therapy for CLL At least 28 days since prior experimental drug or therapy No other concurrent anticancer therapies No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Oral Lenalidomide<br>Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity | Biological: rituximab<br>* IV<br>Drug: lenalidomide<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months | Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. | at 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab | Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count >1500/μL; platelet count >100,000/μL; untransfused hemoglobin concentration >11.0g/dL; lymphocyte count <4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. | 5 years | 
| Number of Participants With Adverse Events on Single Agent CC-5013 | Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail. | 1 year | 
| Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0 | Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab. | 
| Time to Progression for Single Agent CC-5013 | Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. | 5 years | 
| Time to Progression for the Combination Therapy of CC-5013+Rituximab | Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. | Every month up to 6 months and every 3 months thereafter up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory chronic lymphocytic leukemia