Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer
RATIONALE: Pentostatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as 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 pentostatin together with combination chemotherapy and rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of mitoxantrone when given together with pentostatin, cyclophosphamide, and rituximab and to see how well it works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell cancer.
Drug: mitoxantrone hydrochloride
Genetic: fluorescence in situ hybridization
Genetic: gene rearrangement analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: flow cytometry
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Study of Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Previously Treated Patients With Chronic Lymphocytic Leukemia and Other Low Grade B-Cell Neoplasms|
- Overall response including complete response, clinical complete response, nodular response, and partial response [ Time Frame: Prior to cycle 4 and after completion of all therapy ] [ Designated as safety issue: No ]
- Maximum tolerated dose [ Time Frame: After each cycle ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: After each cycle ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2005|
|Study Completion Date:||May 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
|Experimental: Mitoxantrone||Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Biological: sargramostim Drug: cyclophosphamide Drug: mitoxantrone hydrochloride Drug: pentostatin Genetic: fluorescence in situ hybridization Genetic: gene rearrangement analysis Genetic: polymerase chain reaction Genetic: protein expression analysis Other: flow cytometry Procedure: biopsy|
- To determine the dose of mitoxantrone hydrochloride that can be safely administered with pentostatin, cyclophosphamide, and rituximab in patients with previously treated chronic lymphocytic leukemia or other low-grade B-cell malignancies.
- To characterize the toxicity of this regimen in these patients.
- To determine the response rate in patients treated with this regimen.
OUTLINE: This is a phase I, dose-escalation study of mitoxantrone hydrochloride followed by a phase II study.
- Phase I: Patients receive pentostatin IV, cyclophosphamide IV, and mitoxantrone hydrochloride IV on day 1. Patients also receive rituximab IV on day 1 beginning in course 2. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive pentostatin, cyclophosphamide, rituximab, and mitoxantrone hydrochloride (at the maximum tolerated dose determined in phase I) as in phase I.
All patients receive either pegfilgrastim subcutaneously (SC) on days 1-4 following each course or filgrastim or sargramostim SC beginning 2 days after each course until blood counts recover.
Patients undergo blood collection and bone marrow biopsy periodically for assessment of therapy response by biomarker and laboratory studies. Samples are analyzed for molecular genetics for IgH arrangement by PCR and for response by immunoelectrophoresis. Some samples are analyzed for response by flow cytometry or fluorescence in situ hybridization (FISH).
After completion of study treatment, patients are followed every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 63 patients (18 patients for phase I and 45 patients for phase II) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00546377
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Renier Brentjens, MD, PhD||Memorial Sloan-Kettering Cancer Center|
|Principal Investigator:||Andrew D. Zelenetz, MD, PhD||Memorial Sloan-Kettering Cancer Center|