Combination Chemotherapy With or Without G-CSF in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as fludarabine, mitoxantrone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Colony stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of combination chemotherapy. It is not yet known whether giving combination chemotherapy alone is more effective than combination chemotherapy together with G-CSF in treating patients with chronic lymphocytic leukemia. PURPOSE: This randomized phase III trial is studying giving combination chemotherapy together with G-CSF to see how well it works compared to giving combination chemotherapy alone in treating patients with relapsed stage I, stage II, stage III, or stage IV chronic lymphocytic leukemia.

Detailed Description
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OBJECTIVES: Primary Compare the rate of remission, severe infections, and side effects in patients with relapsed advanced chronic lymphocytic leukemia treated with fludarabine, mitoxantrone hydrochloride, and cyclophosphamide with vs without filgrastim. Secondary Compare the overall survival, progression-free survival, and quality of remission in these patients. OUTLINE: This is a multicenter, randomized study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fludarabine IV on days 1-3, mitoxantrone hydrochloride IV on day 1, and cyclophosphamide IV on days 1-3. Arm II: Patients receive fludarabine, mitoxantrone hydrochloride, and cyclophosphamide as in arm I and filgrastim (G-CSF) beginning on day 6 and continuing until blood counts recover. 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 165 patients will be accrued for this study.

Official Title
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Treatment of Advanced Chronic Lymphocytic Leukemia (CLL) Fludarabine, Mitoxantrone and Cyclophosphamide With or Without G-CSF

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Biological: Filgrastim
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Drug: Mitoxantrone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Confirmed relapsed and advanced chronic lymphocytic leukemia (CLL) Binet stage B or C disease with rapid disease progression, enlarged lymph nodes and organs, or severe B-symptoms No prior non-response to fludarabine combination therapy PATIENT CHARACTERISTICS: ECOG performance status 0-3 Life expectancy > 6 months No severe organ dysfunction No other prior or concurrent neoplasm, autoimmune hemolytic anemia, or thrombocytopenia PRIOR CONCURRENT THERAPY: No more than three previous treatment regimens for CLL (fludarabine allowed)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: FCM<br>Fludarabine i.v. (25 mg/m2/d, d1-3) Cyclophosphamide i.v. (200 mg/m2/d, d1-3) Mitoxantrone i.v. (8 mg/m2, d1) q28d, max. 6 cycles | Drug: Fludarabine<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Mitoxantrone<br> <br> |
| Experimental: FCM + G-CSF<br>Fludarabine i.v. (25 mg/m2/d, d1-3) Cyclophosphamide i.v. (200 mg/m2/d, d1-3) Mitoxantrone i.v. (8 mg/m2, d1) Filgrastim (G-CSF) s.c. (5 µg/kg/d beginning on day +6 until neutrophil recovery above 1500/µl.) q28d, max. 6 cycles | Biological: Filgrastim<br> <br> * Other names: Neupogen;Drug: Fludarabine<br> <br> Drug: Cyclophosphamide<br> <br> Drug: Mitoxantrone<br> <br> |

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, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia