Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00337246
Recruitment Status : Completed
First Posted : June 15, 2006
Last Update Posted : August 2, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy with or without rituximab works in treating patients with previously treated chronic lymphocytic leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mitoxantrone hydrochloride Phase 2

Detailed Description:



  • Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia.
  • Determine the overall response rate, defined as complete or partial remission, in these patients.


  • Determine the proportion of patients with undetectable minimal residual disease.
  • Determine the 2-year progression-free survival of these patients.
  • Determine the 2-year overall survival of these patients.
  • Determine the toxicity of this regimen.

OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1.
  • Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1.

NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3.

Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia
Study Start Date : July 2005
Actual Study Completion Date : March 2011

Primary Outcome Measures :
  1. Overall response rate as measured by NCI Response Criteria

Secondary Outcome Measures :
  1. Proportion of patients with undetectable minimal residual disease
  2. Progression-free survival at 2 years
  3. Overall survival at 2 years
  4. Toxicity

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of chronic lymphocytic leukemia requiring therapy
  • Previously treated with ≥ 1 chemotherapeutic regimen


  • WHO performance status 0-2
  • Life expectancy ≥ 12 weeks
  • Creatinine clearance ≥ 30 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile female patients must use effective contraception for 4 weeks before, during, and for 6 months after completion of study treatment
  • Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
  • No history of anaphylaxis after exposure to rat or mouse-derived complementary-determining region (CDR)-grafted humanized monoclonal antibodies
  • No toxicity attributable to purine analogues (e.g., autoimmune hemolytic anemia, neurological toxicity, or allergy)
  • No active infection
  • No other severe (particularly cardiac or pulmonary) diseases or mental disorders that would preclude study participation


  • See Disease Characteristics
  • No prior fludarabine (or other purine analogues) combined with cyclophosphamide and mitoxantrone hydrochloride
  • No prior rituximab, either alone or in combination with chemotherapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00337246

United Kingdom
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Blackpool Victoria Hospital
Blackpool, England, United Kingdom, FY3 8NR
Kent and Canterbury Hospital
Canterbury, England, United Kingdom, CT2 7NR
St Helier Hospital
Carshalton, England, United Kingdom, SM5 1AA
Darent Valley Hospital
Dartford Kent, England, United Kingdom, DA2 8DA
Medway Maritime Hospital
Gillingham Kent, England, United Kingdom, ME7 5NY
Leeds General Infirmary at Leeds Teaching Hospital NHS Trust
Leeds, England, United Kingdom, LS1 3EX
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Liverpool and Broadgreen Hospitals NHS Trust
Liverpool, England, United Kingdom, L7 8XP
Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Christie Hospital NHS Trust
Manchester, England, United Kingdom, M20 4BX
Royal Cornwall Hospital
Truro, Cornwall, England, United Kingdom, TR1 3LJ
Kent and Sussex Hospital
Tunbridge Wells, Kent, England, United Kingdom, TN4 8AT
Wishaw General Hospital
Wishaw, England, United Kingdom, ML2 0DP
Monklands General Hospital
Airdrie, Scotland, United Kingdom, ML6 0JF
University Hospital of Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Cancer Research UK
Study Chair: Peter Hillmen, MD Leeds General Infirmary

Publications of Results: Identifier: NCT00337246     History of Changes
Other Study ID Numbers: CTRU-NCRI-UKCLL01-FCM/FCM-R
CDR0000485181 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: June 15, 2006    Key Record Dates
Last Update Posted: August 2, 2013
Last Verified: May 2007

Keywords provided by National Cancer Institute (NCI):
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV 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
Antimetabolites, Antineoplastic
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors