High-Dose Cytarabine Plus Deoxycytidine in Treating With Acute Myelogenous Leukemia or Other Hematologic Malignancies
Condition: Drug/Agent Toxicity by Tissue/Organ; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Plasmacytoma; Drug-Related Side Effects and Adverse Reactions
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): cytarabine; deoxycytidine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Cytarabine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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