Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and kill more cancer cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients with refractory chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: I. Determine the feasibility and toxicity of using allogeneic peripheral blood stem cell transplantation after intensive, but non-myeloablative chemotherapy with fludarabine/cyclophosphamide in patients with advanced chronic lymphocytic leukemia. II. Determine the engraftment kinetics and degree of chimerism available with this strategy. OUTLINE: This is a nonrandomized, dose-seeking study. Stem cell donors receive G-CSF for 4 days prior to and throughout stem cell harvest. Patients receive intensive chemotherapy with fludarabine and cyclophosphamide for 3 days, with patients entered at increasing doses of both drugs until the dose allowing engraftment is determined. Three days after intensive chemotherapy, allogeneic stem cells are infused. Responding patients who do not experience worse than grade 1 acute graft-vs.-host disease receive additional stem cell infusions after 60 and 120 days. Patients are followed monthly for 4 months, at 6 and 12 months, then yearly for 5 years. PROJECTED ACCRUAL: Up to 25 patients will be entered.

Official Title
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Phase I/II Pilot Study of Allogeneic Peripheral Blood Stem Cell Infusion For Patients With High Risk Chronic Lymphocytic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Biological: Filgrastim (G-CSF)
* Drug: Cyclophosphamide
* Drug: Fludarabine Phosphate
* Procedure: Peripheral Blood Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Advanced chronic lymphocytic leukemia (Rai stage 3 or 4) with at least one of the following high-risk factors: Beta-2 microglobulin 3 or greater Abnormalities of chromosome 17 Other cytogenetic abnormalities Refractory to fludarabine-based chemotherapy or failure to achieve complete remission after 6 courses of a fludarabine-based regimen HLA-identical sibling donor willing and able to undergo apheresis for harvest of G-CSF-stimulated peripheral blood stem cells PATIENT CHARACTERISTICS: Age: 65 and under Performance status: Zubrod 0 or 1 Hematopoietic: Not specified Hepatic: Bilirubin less than 1.5 mg/dL Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No symptomatic cardiac disease Pulmonary: No symptomatic pulmonary disease Other: No active uncontrolled infection PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Chemotherapy + PSCT<br>PSCT = Peripheral Stem Cell Transplantation | Biological: Filgrastim (G-CSF)<br> <br> * Other names: Neupogen;Drug: Cyclophosphamide<br> <br> * Other names: Neosar;Drug: Fludarabine Phosphate<br> <br> * Other names: Fludara;Procedure: Peripheral Blood Stem Cell Transplantation<br> <br> * Other names: Stem Cell Transplant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility + Toxicity of Combination Chemotherapy Plus Peripheral Stem Cell Transplantation |  | Monthly | 

 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, refractory chronic lymphocytic leukemia