Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab and rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. It is not yet known whether fludarabine is more effective when combined with alemtuzumab or with rituximab in treating chronic lymphocytic leukemia. PURPOSE: Randomized phase II trial to compare the effectiveness of combining fludarabine with either alemtuzumab or rituximab in treating patients who have refractory or relapsed B-cell chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Compare the complete response rate in patients with refractory or relapsed B-cell chronic lymphocytic leukemia treated with fludarabine and alemtuzumab vs fludarabine and rituximab. Secondary Compare the overall response rate in patients treated with these regimens. Compare 1-year survival of patients treated with these regimens. Compare time to progression in patients treated with these regimens. Compare duration of response in patients treated with these regimens. Compare the adverse event profile of these regimens in these patients. Compare the molecular response rate in patients treated with these regimens. Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens. Compare the time to complete response in patients treated with these regimens. Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior treatment with fludarabine (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. At least 30 minutes before fludarabine administration, patients receive alemtuzumab subcutaneously (SC) on days 1-5. Arm II: Patients receive fludarabine as in arm I. At least 30 minutes before fludarabine administration, patients receive rituximab IV on days 1 and 4 of course 1 and on day 1 only in subsequent courses. In both arms, treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. An interim assessment is performed during course 4. Patients achieving a partial response or stable disease receive 2 additional courses of therapy (for a total of 6 courses). Patients achieving a complete response (CR) do not receive further treatment beyond CR. Patients are followed weekly for 2 months, monthly for 6 months, every 2 months for 6 months, and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

Official Title
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Phase II Trial Comparing Combination Treatment With Fludarabine and Alemtuzumab to Fludarabine and Rituximab in Patients With B-Cell Chronic Lymphocytic Leukemia Requiring Treatment After First Line Therapy

Conditions
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Leukemia

Intervention / Treatment
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* Biological: alemtuzumab
* Biological: rituximab
* Drug: fludarabine phosphate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as: Peripheral lymphocyte count > 5,000/mm^3 Clonal CD5-, CD19-, and CD23-positive lymphocytes Refractory to OR relapsed after prior first-line therapy No CNS involvement with CLL PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) Hepatitis B surface antigen negative Hepatitis C antibody negative Renal Creatinine ≤ 1.5 times ULN Immunologic No active cytomegalovirus No prior fludarabine-associated autoimmune hemolytic anemia or immune thrombocytopenic purpura No active infection requiring treatment with antibiotic, antiviral, or antifungal agents No prior significant allergic reaction to antibody therapies that required therapy to be discontinued HIV negative Other No active secondary malignancy No other concurrent severe diseases or mental disorders Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy More than 4 weeks since prior alemtuzumab and/or rituximab No prior bone marrow transplantation No concurrent thrombopoietin or pegfilgrastim Chemotherapy More than 3 weeks since prior fludarabine Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other More than 3 months since prior investigational drugs No other concurrent cytotoxic therapy

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
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: alemtuzumab|nan|
|Biological: rituximab|nan|
|Drug: fludarabine phosphate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia