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

This study has been terminated.
(low recruitment)
Information provided by (Responsible Party):
German CLL Study Group Identifier:
First received: December 27, 2006
Last updated: September 23, 2016
Last verified: September 2016

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 Intervention Phase
Chronic Lymphocytic Leukemia
Biological: Filgrastim
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Mitoxantrone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Advanced Chronic Lymphocytic Leukemia (CLL) Fludarabine, Mitoxantrone and Cyclophosphamide With or Without G-CSF

Resource links provided by NLM:

Further study details as provided by German CLL Study Group:

Enrollment: 83
Study Start Date: July 1999
Study Completion Date: September 2007
Primary Completion Date: September 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Neupogen
Drug: Fludarabine Drug: Cyclophosphamide Drug: Mitoxantrone

Detailed Description:



  • 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.


  • 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.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • ECOG performance status 0-3
  • Life expectancy > 6 months
  • No severe organ dysfunction
  • No other prior or concurrent neoplasm, autoimmune hemolytic anemia, or thrombocytopenia


  • No more than three previous treatment regimens for CLL (fludarabine allowed)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00416910

Sponsors and Collaborators
German CLL Study Group
Principal Investigator: Michael Hallek, MD Medizinische Universitaetsklinik I at the University of Cologne
  More Information

Additional Information:
Responsible Party: German CLL Study Group Identifier: NCT00416910     History of Changes
Other Study ID Numbers: GCLLSG-CLL6  CDR0000455571  EU-20558  AMGEN-GCLLSG-CLL6  MEDAC-GCLLSG-CLL6 
Study First Received: December 27, 2006
Last Updated: September 23, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by German CLL Study Group:
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on October 27, 2016