Fludarabine and Thalidomide in Treating Patients With Newly Diagnosed 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. Biological therapies such as thalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Combining fludarabine with thalidomide may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of thalidomide when given together with fludarabine and to see how well they work in treating patients with newly diagnosed B-cell chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Determine the safety and efficacy of fludarabine and thalidomide in patients with newly diagnosed B-cell chronic lymphocytic leukemia. Determine the overall response rate (complete and partial) in patients treated with this regimen. Determine the duration of response in patients treated with this regimen. OUTLINE: This is an open-label, phase I, dose-escalation study of thalidomide followed by a phase II study. Phase I: Beginning on day 1, patients receive oral thalidomide once daily for up to 6 months. Beginning on day 7, patients also receive fludarabine IV over 30 minutes daily for 5 days. Treatment with fludarabine repeats every 28-35 days for up to 6 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of thalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive fludarabine and thalidomide as in phase I at the MTD. Patients are followed at 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years. PROJECTED ACCRUAL: Up to 45 patients (≥ 9 for the phase I portion and ≤ 36 for the phase II portion) will be accrued for this study within 8 years.

Official Title
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A Phase I/II Study of Fludarabine Plus Thalidomide as Frontline Therapy for Newly Diagnosed Patients With Chronic Lymphocytic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: fludarabine phosphate
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL) based on the following criteria: Peripheral blood lymphocytosis > 5,000/mm^3 Co-expression of CD5, CD19 or CD20, and CD23 surface antigens Clonal kappa or lambda light chain expression No recurrent or refractory CLL No other lymphoproliferative diseases or diseases due to transformation of CLL, such as prolymphocytic leukemia or Richter's syndrome PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy At least 12 weeks Hematopoietic See Disease Characteristics Hepatic Bilirubin < 1.5 mg/dL AST < 2.5 times upper limit of normal Renal Creatinine ≤ 1.5 mg/dL Cardiovascular No cardiac arrhythmia within the past 6 months No myocardial infarction within the past 6 months Other Not pregnant or nursing Negative pregnancy test Fertile patients must use at least 1 highly active and 1 additional method of contraception for 4 weeks before, during, and for at least 4 weeks after study treatment Patients must have sufficient mental capacity to understand the study explanation and provide informed consent No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No active serious infection uncontrolled by antibiotics No medical condition or reason that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other No prior therapy for CLL

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: Dose escalation<br>Thalidomide (100 mg/day, 200 mg/day, or 300 mg/day) on Day 1 followed by Fludarabine 25 mg/m2/day for 5 days starting on Day 7 (cycle = 28 days | Drug: fludarabine phosphate<br>* Given IV<br>Drug: thalidomide<br>* Orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Responders (Complete and Partial Response) | Criteria for response were based on the Revised National Cancer Institute-sponsored Working Group Guidelines for response, which includes clinical, hematologic, and bone marrow features (Cheson, B.D., et al., National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990-97.) | 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years | 
| Duration of Response |  | 4 weeks, every 3 months for 2 years, and then every 4 months for 2 years | 

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