Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers

June 24, 2013 updated by: Memorial Sloan Kettering Cancer Center

A Phase I-II Study of Pentostatin With Cyclophosphamide for Previously Treated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining pentostatin, cyclophosphamide, and rituximab in treating patients who have chronic lymphocytic leukemia or other B-cell cancers that have been treated previously.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the dose of cyclophosphamide, with filgrastim (G-CSF) support, that can be safely administered with pentostatin and rituximab in patients with previously treated intermediate- or high-risk chronic lymphocytic leukemia or other low-grade B-cell malignancies. (Phase I closed to accrual effective 11/27/2001.)
  • Characterize the toxicity of this regimen in these patients.
  • Determine the incidence of response in these patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of cyclophosphamide (CTX).

  • Phase I: Patients receive CTX IV followed by pentostatin IV on day 1 of course 1. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 3 and continuing until blood counts recover. During the second and subsequent courses, patients receive CTX IV, pentostatin IV, and rituximab IV on day 1. Patients also receive G-CSF as in course 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with at least a partial response after the third course receive an additional 3 courses.

Cohorts of 3-6 patients receive escalating doses of CTX until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

(Phase I closed to accrual effective 11/27/2001.)

  • Phase II: Patients receive CTX at the recommended phase II dose and treatment as above.

Patients are followed at least every 3 months for 1 year and then periodically thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for the phase I portion of this study. (Phase I closed to accrual effective 11/27/2001.) A total of 14-30 patients will be accrued for the phase II portion of this study within 2.5 years.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Intermediate- or high-risk chronic lymphocytic leukemia (CLL) as defined by the three-stage Rai system

    • Rai intermediate disease must be active disease (including weight loss, fatigue, fevers, evidence of progressive marrow failure, splenomegaly, progressive lymphadenopathy, and progressive lymphocytosis with a rapid doubling time)
  • Other low-grade B-cell neoplasms, including small lymphocytic lymphoma (and its variants), Waldenstrom's macroglobulinemia, and follicular lymphoma allowed
  • Autoimmune hemolytic anemia or autoimmune thrombocytopenia allowed regardless of disease stage
  • B-cells demonstrated by immunophenotypic (or immunohistochemical) analysis of the malignant lymphocytes
  • Must be previously treated
  • For CLL, absolute lymphocytosis in the blood at least 5,000 lymphocytes/mm^3 OR
  • Bone marrow lymphocytosis at least 30% of all nucleated cells
  • No Rai intermediate-risk disease that meets the criteria of Montserrat "smoldering leukemia" NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • More than 4 weeks

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL

Renal:

  • Creatinine no greater than 2.0 mg/dL

Other:

  • No active infections requiring systemic antibiotics
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy
  • Concurrent intravenous immunoglobulin allowed
  • Concurrent epoetin alfa allowed

Chemotherapy:

  • At least 4 weeks since prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • Concurrent prednisone therapy allowed as long as dose is stable or decreasing over the past 4 weeks
  • No increase in prednisone therapy while on study

Radiotherapy:

  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy

Surgery:

  • Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1998

Primary Completion (Actual)

October 1, 2005

Study Completion (Actual)

October 1, 2005

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 25, 2013

Last Update Submitted That Met QC Criteria

June 24, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-083
  • CDR0000066751 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-G98-1482

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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