Pentostatin, Cyclophosphamide, and Rituximab in Treating Patients With Chronic Lymphocytic Leukemia or Other B-cell Cancers
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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 |
| Estimated Enrollment: | 60 |
| Study Start Date: | September 1998 |
| Primary Completion Date: | October 2005 (Final data collection date for primary outcome measure) |
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 |
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| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | |
| New York, New York, United States, 10021 | |
| 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: | CDR0000066751, MSKCC-98083, NCI-G98-1482 |
| Study First Received: | November 1, 1999 |
| Last Updated: | February 19, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
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 Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclophosphamide Rituximab Pentostatin Lenograstim |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Adenosine Deaminase Inhibitors Enzyme Inhibitors Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 16, 2013