Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia
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.
Drug: fludarabine phosphate
Drug: mitoxantrone hydrochloride
|Study Design:||Allocation: Randomized
Masking: 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|
- Overall response rate as measured by NCI Response Criteria [ Designated as safety issue: No ]
- Proportion of patients with undetectable minimal residual disease [ Designated as safety issue: No ]
- Progression-free survival at 2 years [ Designated as safety issue: No ]
- Overall survival at 2 years [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
|Study Start Date:||July 2005|
|Study Completion Date:||March 2011|
- 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.
|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, 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|
|Study Chair:||Peter Hillmen, MD||Leeds General Infirmary|