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
- 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
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response including complete response, clinical complete response, nodular response, and partial response
Prior to cycle 4 and after completion of all therapy
Renier Brentjens, MD, PhD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|