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High-Dose Cytarabine Plus Deoxycytidine in Treating Patients With Acute Myelogenous Leukemia or Other Hematologic Malignancies
This study has been completed.
First Received: August 3, 2000   Last Updated: May 9, 2009   History of Changes
Sponsors and Collaborators: Massey Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002818
  Purpose

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.


Condition Intervention Phase
Drug/Agent Toxicity by Tissue/Organ
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Drug: cytarabine
Drug: deoxycytidine
Phase I

Study Type: Interventional
Study Design: Supportive Care
Official Title: PHASE I AND CLINICAL PHARMACOKINETIC DE-ESCALATION STUDY OF 2'-DEOXYCYTIDINE (IND 28108) ADMINISTERED AS A 120-HOUR CONTINUOUS INFUSION IN CONJUNCTION WITH A 96-HOUR CONTINUOUS INFUSION OF HIGH-DOSE 1-BETA-D ARABINOFURANOSYLCYTOSINE (Ara-C) IN PATIENTS WITH REFRACTORY ACUTE MYELOGENOUS LEUKEMIA AND OTHER HEMATOLOGIC MALIGNANCIES

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: February 1995
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002818

Locations
United States, Virginia
Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Massey Cancer Center
Investigators
Study Chair: Steven Grant, MD Massey Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000064976, MCV-MCC-9409-2CC, VCU-FDR000637, NCI-V96-0966
Study First Received: August 3, 2000
Last Updated: May 9, 2009
ClinicalTrials.gov Identifier: NCT00002818     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Anti-Infective Agents
Blast Crisis
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Follicular Lymphoma
Acute Myelocytic Leukemia
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Blood Coagulation Disorders
Leukemia, Myeloid
Multiple Myeloma
B-cell Lymphomas
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors
Hematologic Neoplasms
Blood Protein Disorders
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Paraproteinemias
Leukemia, Myeloid, Acute
Hemostatic Disorders

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Hematologic Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Leukemia, Myeloid, Acute
Hemostatic Disorders
Leukemia
Hemorrhagic Disorders
Neoplasms by Site
Therapeutic Uses
Cardiovascular Diseases
Lymphoma
Cytarabine
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Vascular Diseases
Leukemia, Myeloid
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Multiple Myeloma
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 02, 2009