A Phase I-II Study of Pentostatin With Cyclophosphamide for Previously Treated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia
filgrastim
+ rituximab
+ cyclophosphamide
Blood Protein Disorders+24
+ Cardiovascular Diseases
+ Chronic Disease
Treatment Study
Summary
Study start date: September 1, 1998
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.60 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Memorial Sloan-Kettering Cancer Center
New York, United StatesOpen Memorial Sloan-Kettering Cancer Center in Google Maps