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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
cyclophosphamide
pentostatin
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring B-cell chronic lymphocytic leukemia, stage I small lymphocytic lymphoma, stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cyclophosphamide, pentostatin & rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Objective Response
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.

Secondary Outcome Measures

Full Information

First Posted
October 5, 2007
Last Updated
July 13, 2017
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI), Astex Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00541034
Brief Title
Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia
Official Title
Phase II Study of Pentostatin With Cyclophosphamide and Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI), Astex Pharmaceuticals, Inc.

4. Oversight

5. Study Description

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, 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
B-cell chronic lymphocytic leukemia, stage I small lymphocytic lymphoma, stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cyclophosphamide, pentostatin & rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
pentostatin
Primary Outcome Measure Information:
Title
Overall Objective Response
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicole Lamanna, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Renier Brentjens, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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