Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): filgrastim; pegfilgrastim; rituximab; sargramostim; cyclophosphamide; mitoxantrone hydrochloride; pentostatin; fluorescence in situ hybridization; gene rearrangement analysis; polymerase chain reaction; protein expression analysis; flow cytometry; biopsy
Intervention type(s): Biological; Biological; Biological; Biological; Drug; Drug; Drug; Genetic; Genetic; Genetic; Genetic; Other; Procedure
Intervention MeSH terms: Cyclophosphamide; Rituximab; Mitoxantrone; Pentostatin; Sargramostim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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