RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Deoxycytidine may protect patients from the side effects of
PURPOSE: Phase I trial to study the effectiveness of high-dose cytarabine given with
deoxycytidine in treating patients who have refractory acute myelogenous leukemia or other
lymphoma or leukemia.
OBJECTIVES: I. Estimate the lowest dose of deoxycytidine (dC) that can be given as a host
protective agent in conjunction with high dose cytarabine (HD ARA-C) in patients with
refractory acute myelogenous leukemia or other hematologic malignancies. II. Determine the
maximum tolerated dose and dose-limiting toxic effects of HD ARA-C/dC in these patients.
III. Characterize the pharmacokinetics of continuously administered HD ARA-C/dC in these
patients. IV. Characterize, when possible, the pharmacodynamics of HD ARA-C, dC, and their
metabolites in blasts obtained from leukemic patients participating in this trial. V.
Recommend the lowest possible dose of dC that can be given in combination with HD ARA-C in
future phase II trials.
OUTLINE: This is a dose escalation study. Patients receive deoxycytidine IV over 120 hours.
Beginning 12 hours after initiation of deoxycytidine, patients receive high dose cytarabine
IV over 96 hours. Patients achieving complete response receive no further therapy. Patients
achieving partial response or initial complete response and subsequent relapse receive an
additional course of therapy. Cohorts of 3-6 patients receive escalating doses of
deoxycytidine and high dose cytarabine until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose
PROJECTED ACCRUAL: Approximately 24-30 patients will be accrued for this study.
DISEASE CHARACTERISTICS: One of the following histologically documented hematologic
malignancies: Acute myelogenous leukemia Failed or relapsed following conventional dose
chemotherapy (e.g., doxorubicin, cytarabine) or high dose cytarabine (HD ARA-C) Chronic
myelogenous leukemia in blast crisis that has failed at least 1 conventional antileukemic
regimen Acute lymphoblastic leukemia (ALL) that is relapsed following or initially
refractory to conventional therapy Failed at least 1 salvage regimen for ALL Disease
refractory to conventional HD ARA-C allowed Primarily refractory or relapsed Hodgkin's or
non-Hodgkin's lymphoma Failed at least 1 conventional second or third generation regimen
(e.g., ProMACE-CytaBOM) Refractory multiple myeloma Not eligible for protocols of higher
priority and no alternative forms of therapy available that offer a reasonable chance of
palliation or cure
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life
expectancy: At least 8 weeks Hematopoietic: Not specified Hepatic: Bilirubin less than 3
mg/dL Renal: Creatinine clearance at least 40 mL/min Pulmonary: Pulse oximetry greater
than 88% in patients with a history of pulmonary disease Other: No major concurrent
disease that renders patient a poor medical risk No uncontrolled infection Disease related
fever allowed at investigator's discretion No mental incapacity that precludes informed
consent No incarcerated patients Not pregnant Effective contraception required of fertile
PRIOR CONCURRENT THERAPY: Not specified Biologic therapy: Not specified Chemotherapy: At
least 3 weeks since prior chemotherapy (24 hours since hydroxyurea) and recovered
Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to 30% or more of
bone marrow At least 4 weeks since prior radiotherapy and recovered Surgery: Not specified