Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating chronic lymphocytic leukemia. PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy with or without rituximab works in treating patients with previously treated chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia. Determine the overall response rate, defined as complete or partial remission, in these patients. Secondary Determine the proportion of patients with undetectable minimal residual disease. Determine the 2-year progression-free survival of these patients. Determine the 2-year overall survival of these patients. Determine the toxicity of this regimen. OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1. Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1. NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3. Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Official Title
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A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide
* Drug: fludarabine phosphate
* Drug: mitoxantrone hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of chronic lymphocytic leukemia requiring therapy Previously treated with ≥ 1 chemotherapeutic regimen PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy ≥ 12 weeks Creatinine clearance ≥ 30 mL/min Not pregnant or nursing Negative pregnancy test Fertile female patients must use effective contraception for 4 weeks before, during, and for 6 months after completion of study treatment Fertile male patients must use effective contraception during and for 6 months after completion of study treatment No history of anaphylaxis after exposure to rat or mouse-derived complementary-determining region (CDR)-grafted humanized monoclonal antibodies No toxicity attributable to purine analogues (e.g., autoimmune hemolytic anemia, neurological toxicity, or allergy) No active infection No other severe (particularly cardiac or pulmonary) diseases or mental disorders that would preclude study participation PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior fludarabine (or other purine analogues) combined with cyclophosphamide and mitoxantrone hydrochloride No prior rituximab, either alone or in combination with chemotherapy
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: rituximab|nan|
|Drug: cyclophosphamide|nan|
|Drug: fludarabine phosphate|nan|
|Drug: mitoxantrone hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate as measured by NCI Response Criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with undetectable minimal residual disease |  |  | 
| Progression-free survival at 2 years |  |  | 
| Overall survival at 2 years |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia