High-Dose Cytarabine Plus Deoxycytidine in Treating With Acute Myelogenous Leukemia or Other Hematologic Malignancies

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002818
• Other study ID #: CDR0000064976
• Secondary ID: P30CA016059MCV-M
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2000
• Last updated: December 10, 2015
• Start date: February 1995
• Est. completion date: February 2001

Study information

• Verified date: December 2015
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 2001
• Est. primary completion date: February 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Drug/Agent Toxicity by Tissue/Organ
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• cytarabine

• deoxycytidine

Locations

Country	Name	City	State
United States	Massey Cancer Center	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,