Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

July 13, 2017 updated by: Memorial Sloan Kettering Cancer Center

Phase II Study of Pentostatin With Cyclophosphamide and Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia

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, 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 cyclophosphamide and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving pentostatin together with cyclophosphamide and rituximab works in treating patients with previously untreated chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • To determine the frequency of response in patients with previously untreated, intermediate- or high-risk B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab.
  • To characterize the toxicity of this regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at least every 3 months for 1 year.

Study Type

Interventional

Enrollment (Actual)

49

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, 10065
        • 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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic lymphocytic leukemia (CLL), as evidenced by an absolute lymphocytosis in the blood of at least 5,000 lymphocytes per microliter OR bone marrow lymphocytosis ≥ 30% of all nucleated cells

    • Previously untreated disease

  • Meets 1 of the following risk criteria as defined by the three-stage Rai system

    • Intermediate-risk disease

      • Must meet the criteria for active disease as defined by the NCI Working Group guidelines including the following:

        • Weight loss
        • Fatigue
        • Fevers
        • Evidence of progressive marrow failure
        • Splenomegaly
        • Progressive lymphadenopathy
        • Progressive lymphocytosis with a rapid doubling time
    • High-risk disease
  • Malignant lymphocytes must demonstrate B-cells via immunophenotypic or immunohistochemical analysis
  • Patients with small lymphocytic lymphoma (CLL type) are eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Karnofsky performance status 60-100%
  • Total bilirubin ≤ 2.0 mg/dL (patients with Gilbert disease or autoimmune hemolytic anemia should have an evaluation for other causes of hyperbilirubinemia, but if none are found they may be enrolled regardless of serum bilirubin)
  • Total creatinine ≤ 2.0 mg/dL OR creatinine clearance > 50 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are eligible for treatment on this protocol regardless of disease stage

Exclusion criteria:

  • Significant active infections

  • Ongoing hepatitis B infection, specifically hepatitis B antigen or surface antigen positivity

    • Patients who are hepatitis B antibody positive are eligible for this protocol

PRIOR CONCURRENT THERAPY:

  • Concurrent prednisone allowed provided it is used as brief courses (≤ 7 days) for inflammatory conditions unrelated to CLL
  • No prior cytotoxic therapy or rituximab for this cancer
  • No concurrent radiotherapy or other chemotherapy

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
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: cyclophosphamide, pentostatin & rituximab
Patients receive cyclophosphamide IV followed by pentostatin IV on day 1 in course 1. Beginning in course 2 and in all subsequent courses, patients receive cyclophosphamide IV on day 1, pentostatin IV on day 1, and rituximab IV on day 1 or on days 1 and 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide
Biological: rituximab
Drug: pentostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Objective Response
Time Frame: 2 years
The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment, will be repeated to document the degree of maximal response.
2 years

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)
Astex Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Nicole Lamanna, MD, Memorial Sloan Kettering Cancer Center

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.

Helpful Links

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

May 1, 2005

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

October 5, 2007

First Submitted That Met QC Criteria

October 5, 2007

First Posted (Estimate)

October 8, 2007

Study Record Updates

Last Update Posted (Actual)

August 11, 2017

Last Update Submitted That Met QC Criteria

July 13, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05-051
  • P30CA008748 (U.S. NIH Grant/Contract)
  • MSKCC-05051

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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