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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

Phase 1
18 Years
Not Enrolling
Drug/Agent Toxicity by Tissue/Organ, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

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

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.

Inclusion 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

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

Type of Study:


Study Design:

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

Principal Investigator

Steven Grant, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massey Cancer Center


United States: Federal Government

Study ID:




Start Date:

February 1995

Completion Date:

February 2001

Related Keywords:

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



Massey Cancer Center Richmond, Virginia  23298-0037