Clinical trial NCT00546377
Conditions: Leukemia Lymphoma
Keywords: B-cell chronic lymphocytic leukemia Waldenstrom macroglobulinemia recurrent mantle cell lymphoma recurrent small lymphocytic lymphoma refractory chronic lymphocytic leukemia recurrent marginal zone lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma
Sponsor: Memorial Sloan Kettering Cancer Center
Start date: 2005-07-01; Completion date: 2014-05-01
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: None
Interventions: intervention 1: filgrastim intervention 2: pegfilgrastim intervention 3: rituximab intervention 4: sargramostim intervention 5: cyclophosphamide intervention 6: mitoxantrone hydrochloride intervention 7: pentostatin intervention 8: fluorescence in situ hybridization intervention 9: gene rearrangement analysis intervention 10: polymerase chain reaction intervention 11: protein expression analysis intervention 12: flow cytometry intervention 13: biopsy
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None intervention 10: None intervention 11: None intervention 12: None intervention 13: None

Protocol documents: