Arsenic Trioxide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, cytarabine, and idarubicin,
      work in different ways to stop cancer cells from dividing so they stop growing or die.
      Combining more than one drug may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide
      when given together with cytarabine and idarubicin in treating patients with acute myeloid
      leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the maximum tolerated dose and/or biologically effective dose of arsenic
           trioxide followed by high-dose cytarabine and idarubicin in patients with previously
           untreated de novo or secondary acute myeloid leukemia.

      OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients are stratified
      according to timing of accrual (before November 2002 vs since November 2002).

      Patients receive arsenic trioxide IV over 1 hour on day 1 followed by high-dose cytarabine IV
      over 1 hour every 12 hours on days 1-6 and idarubicin IV over 30 minutes on days 2-4
      (immediately after doses 3, 5 and 7 of cytarabine). Patients also receive filgrastim (G-CSF)
      subcutaneously beginning 12 hours after the last dose of chemotherapy and continuing until
      blood counts recover.

      Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum
      tolerated dose (MTD), current dose used for myelodysplastic syndromes or acute promyelocytic
      leukemia, or biologically effective dose is reached. The MTD is defined as the dose preceding
      that at which 2 of 6 patients experience dose-limiting toxicity. The biologically effective
      dose is defined as the dose at which 3 patients with constitutive STAT3 activity have the
      activity negated after the first dose of arsenic trioxide.

      PROJECTED ACCRUAL: A maximum of 40 patients (6 for stratum I [accrued before November 2002]
      and 34 for stratum II [accrued since November 2002] will be accrued for this study within 3
      years.
    

Intervention name(s): filgrastim; arsenic trioxide; cytarabine; idarubicin
Intervention type(s): Biological; Drug; Drug; Drug
Intervention description(s): Subcutaneously beginning 12 hours after the last dose of chemotherapy and continuing until blood counts recover.; IV over 1 hour on day 1; IV over 1 hour every 12 hours on days 1-6; IV over 30 minutes on days 2-4 (immediately after doses 3, 5 and 7 of cytarabine).
Intervention MeSH terms: Cytarabine; Idarubicin; Arsenic Trioxide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; untreated adult acute myeloid leukemia; secondary acute myeloid leukemia