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

Primary Purpose

Leukemia, Lymphoma

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

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Waldenström macroglobulinemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma

Eligibility Criteria

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

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
June 24, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003658
Brief Title
Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers
Official Title
A Phase I-II Study of Pentostatin With Cyclophosphamide for Previously Treated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
October 2005 (Actual)
Study Completion Date
October 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
Waldenström macroglobulinemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, recurrent small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
pentostatin

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Adam Weiss, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16520464
Citation
Lamanna N, Kalaycio M, Maslak P, Jurcic JG, Heaney M, Brentjens R, Zelenetz AD, Horgan D, Gencarelli A, Panageas KS, Scheinberg DA, Weiss MA. Pentostatin, cyclophosphamide, and rituximab is an active, well-tolerated regimen for patients with previously treated chronic lymphocytic leukemia. J Clin Oncol. 2006 Apr 1;24(10):1575-81. doi: 10.1200/JCO.2005.04.3836. Epub 2006 Mar 6.
Results Reference
result
PubMed Identifier
12663715
Citation
Weiss MA, Maslak PG, Jurcic JG, Scheinberg DA, Aliff TB, Lamanna N, Frankel SR, Kossman SE, Horgan D. Pentostatin and cyclophosphamide: an effective new regimen in previously treated patients with chronic lymphocytic leukemia. J Clin Oncol. 2003 Apr 1;21(7):1278-84. doi: 10.1200/JCO.2003.08.100.
Results Reference
result

Learn more about this trial

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

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