Mitomycin and Mitoxantrone in Treating Patients With Acute Myelogenous Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
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. Some cancers become resistant to chemotherapy drugs. Combining
      mitomycin with a chemotherapy drug may reduce resistance to the drug and allow the cancer
      cells to be killed.

      PURPOSE: Phase I trial to study the effectiveness of mitomycin and mitoxantrone in treating
      patients with acute myelogenous leukemia and to determine whether mitomycin can reduce the
      cancer's resistance to chemotherapy.
    

Detailed description: 
      OBJECTIVES: I. Determine whether a single mitomycin C treatment will suppress expression of
      one or more proteins associated with the multidrug resistance phenotype in leukemia cells of
      patients with refractory acute myelogenous leukemia. II. Determine the maximum tolerated dose
      of a combination of mitomycin C followed 72 hours later by a single dose of mitoxantrone in
      patients with acute myelogenous leukemia with GM-CSF support. III. Determine the toxicity
      profile and pharmokinetics for these combinations of mitomycin C and mitoxantrone. IV.
      Determine the ability of this regimen to induce complete response in patients with primary
      resistant or refractory acute myelogenous leukemia.

      OUTLINE: Patients receive mitomycin C by IV bolus on day 1 of treatment. Patients receive
      mitoxantrone beginning on day 4. One patient each is entered at the first and second dose
      levels. Dose escalation of mitoxantrone continues in the absence of toxicity. If the patient
      experiences toxicity at level 1 or 2, then 2 additional patients are entered at that tier.
      Three patients are entered at all subsequent tiers. At these tiers, if no toxicity is
      observed, escalation continues. If 1 of the 3 patients experiences toxicity, an additional 3
      patients are enrolled at the same dose. If none of these additional patients experiences
      toxicity, escalation continues; however, if 1 patient has toxicity, the trial is stopped. If
      2 or more have toxicities, the dose is de-escalated. If 2 or more of the original 3 patients
      have toxicities, the dose is de-escalated. On day 15, patients are treated with sargramostim
      (GM-CSF) intravenously over 4 hours if the bone marrow is free of residual leukemia; GM-CSF
      treatment continues until the ANC is greater than 1,500/mm3 for 3 consecutive days.

      PROJECTED ACCRUAL: For the pilot study of mitomycin C modulation of multidrug resistance
      proteins, 12 patients will be accrued. For the phase I study of mitomycin C and mitoxantrone,
      at least 17 patients will be entered.
    

Intervention name(s): sargramostim; mitomycin C; mitoxantrone hydrochloride
Intervention type(s): Biological; Drug; Drug
Intervention MeSH terms: Mitoxantrone; Mitomycins; Mitomycin; Sargramostim
Primary purpose: Treatment
Keywords: recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia