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

German CLL Study Group

Status and phase: Terminated; Phase 3

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Mitoxantrone; Drug: Fludarabine; Biological: Filgrastim; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT00416910

CDR0000455571 (Registry Identifier)

GCLLSG-CLL6

MEDAC-GCLLSG-CLL6

EU-20558

AMGEN-GCLLSG-CLL6

Details and patient eligibility

About

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.

Full 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.

Enrollment: 83 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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83 participants in 2 patient groups

FCM

Active Comparator group

Description:

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

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Drug: Mitoxantrone

FCM + G-CSF

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Biological: Filgrastim

Drug: Fludarabine

Drug: Mitoxantrone