Clinical trial NCT00002818: High-Dose Cytarabine Plus Deoxycytidine in Treating With Acute Myelogenous Leukemia or Other Hematologic Malignancies
Official title: Phase I and Clinical Pharmacokinetic De-Escalation Study of 2'-Deoxycitidine Administered as a Continuous Infusion in Conjunction With a Continuous Infusion of High-Dose ARA-C in Patients With Refractory Acute Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug/Agent Toxicity by Tissue/Organ
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Keywords: recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
drug/agent toxicity by tissue/organ
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 high-dose cytarabine.

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.

Detailed description: 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 limiting toxicities.

PROJECTED ACCRUAL: Approximately 24-30 patients will be accrued for this study.

Eligibility criteria: 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 women

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Steven Grant, MD
role: STUDY_CHAIR
References: