Fludarabine With or Without Cyclophosphamide in Treating Patients With Advanced Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving fludarabine together with cyclophosphamide is more effective than fludarabine alone in treating chronic lymphocytic leukemia. PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide to see how well it works compared to fludarabine alone in treating patients with advanced chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Compare the progression-free survival, as well the overall survival and duration of remission in patients with previously untreated, advanced chronic lymphocytic leukemia treated with fludarabine with versus without cyclophosphamide. Secondary Compare the incidence of side effects and quality of life of patients treated with these drugs. OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment arms Arm I: Patients receive fludarabine IV on days 1-5. Arm II: Patients receive fludarabine IV and cyclophosphamide IV on days 1-3. In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study.

Official Title
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Fludarabine Versus Fludarabine Plus Cyclophosphamide in First Line Therapy of Younger Patients (Up to 65 Years) With Advanced Chronic Lymphocytic Leukemia (CLL)

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Fludarabine plus Cyclophosphamide
* Drug: Fludarabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Confirmed diagnosis of previously untreated chronic lymphocytic leukemia (CLL) Binet stage C and stage B are acceptable if there is rapid disease progression, symptoms of enlarged lymph nodes and organs, or severe B-symptoms Binet stage A is acceptable, if there are B-symptoms PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 6 months No severe organ dysfunction No other previous or concurrent neoplasms, autoimmune hemolytic anemia, or thrombocytopenia PRIOR CONCURRENT THERAPY: No prior or concurrent chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fludarabine plus Cyclophosphamide<br> | Drug: Fludarabine plus Cyclophosphamide<br>* fludarabine at a dose of 25 mg/m2, administered intravenously daily over 30 minutes for 5 days, or fludarabine dosed at 30 mg/m2, administered intravenously daily over 30 minutes for 3 days, plus cyclophosphamide dosed at 250 mg/m2, administered intravenously daily over 30 minutes for 3 days, repeated every 28 days for a maximum of 6 courses<br>|
| Active Comparator: Fludarabine<br> | Drug: Fludarabine<br>* fludarabine at a dose of 25 mg/m2, administered intravenously daily over 30 minutes for 5 days, or fludarabine dosed at 30 mg/m2, administered intravenously daily over 30 minutes for 3 days, , repeated every 28 days for a maximum of 6 courses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | date of randomization until progression of disease or death of any cause | 18 Month after end of treatment of the last patient | 
| Overall survival | Date of randomization until date of death | 18 Month after end of treatment of the last patient | 
| Duration of remission | Clinical response was defined according to the guidelines of the NCI-sponsored workshop | 18 Month after end of treatment of the last patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of side effects | Toxic effects of treatment were evaluated according to the Common Toxicity Criteria (CTC 1.0) | up to 28 days after the last dose of study medication | 
| Quality of life | EORTC QUOL Questionnaire | 18 Month after end of treatment of the last patient | 

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