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

Sponsor

German CLL Study Group (Other)

Overall Status

Terminated

CT.gov ID

NCT00416910

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Biological: Filgrastim Drug: Fludarabine Drug: Cyclophosphamide Drug: Mitoxantrone	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Sep 1, 2003

Actual Study Completion Date :

Sep 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: FCM 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 Drug: Cyclophosphamide Drug: Mitoxantrone
Experimental: FCM + G-CSF 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 Other Names: Neupogen Drug: Fludarabine Drug: Cyclophosphamide Drug: Mitoxantrone

Arm

Intervention/Treatment

Active Comparator: FCM

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

Drug: Cyclophosphamide

Drug: Mitoxantrone

Experimental: FCM + G-CSF

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

Other Names:

Neupogen

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: Mitoxantrone

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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