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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00003658
First received: November 1, 1999
Last updated: June 24, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: pentostatin
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I-II Study of Pentostatin With Cyclophosphamide for Previously Treated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Estimated Enrollment: 60
Study Start Date: September 1998
Study Completion Date: October 2005
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003658

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Mark Adam Weiss, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00003658     History of Changes
Other Study ID Numbers: 98-083, CDR0000066751, NCI-G98-1482
Study First Received: November 1, 1999
Last Updated: June 24, 2013
Health Authority: United States: Federal Government

Keywords provided by Memorial Sloan-Kettering Cancer Center:
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Pentostatin
Rituximab
Adenosine Deaminase Inhibitors
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014