Pentostatin, Cyclophosphamide, Rituximab, and Mitoxantrone in Treating Patients With Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Cancer

NCT ID: NCT00546377

Last Updated: 2016-05-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2014-05-31

Brief Summary

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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

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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.

Conditions

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Leukemia Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Mitoxantrone

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

pegfilgrastim

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

mitoxantrone hydrochloride

Intervention Type DRUG

pentostatin

Intervention Type DRUG

fluorescence in situ hybridization

Intervention Type GENETIC

gene rearrangement analysis

Intervention Type GENETIC

polymerase chain reaction

Intervention Type GENETIC

protein expression analysis

Intervention Type GENETIC

flow cytometry

Intervention Type OTHER

biopsy

Intervention Type PROCEDURE

Interventions

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filgrastim

Intervention Type BIOLOGICAL

pegfilgrastim

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

mitoxantrone hydrochloride

Intervention Type DRUG

pentostatin

Intervention Type DRUG

fluorescence in situ hybridization

Intervention Type GENETIC

gene rearrangement analysis

Intervention Type GENETIC

polymerase chain reaction

Intervention Type GENETIC

protein expression analysis

Intervention Type GENETIC

flow cytometry

Intervention Type OTHER

biopsy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Must have undergone consultation with the primary investigator or his/her designee prior to study entry
* No significant active infections
* No ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

* Hepatitis B antibody-positive patients are eligible

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* The following concurrent medications are allowed:

* Intravenous immunoglobulin (IVIG)
* Erythropoietin, darbepoetin, filgrastim, or sargramostim
* Cyclosporine (only for patients with cellular immune cytopenias \[i.e., pure red cell aplasia\]), with required consultation of the principle investigator or designee
* Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
* No concurrent chemotherapy or radiotherapy
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Renier Brentjens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Andrew D. Zelenetz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

Other Identifiers

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MSKCC-05077

Identifier Type: -

Identifier Source: secondary_id

05-077

Identifier Type: -

Identifier Source: org_study_id

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