Amifostine and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

OBJECTIVES:

• Determine whether amifostine provides systemic protection against the nonhematologic side effects of idarubicin (IDR) during induction therapy of acute myeloid leukemia (AML), allowing the dose of idarubicin to be escalated.
• Determine the maximum tolerated dose of idarubicin when amifostine is used as a chemotherapy protectant.
• Determine the incidence and severity of dose limiting hypotension in patients receiving amifostine and the ability to offset this side effect with vasoconstrictive agents.
• Determine whether any additional side effects of amifostine are dose limiting in patients with AML treated with IDR and cytarabine (ARA-C).
• Monitor the frequency of alopecia, mucositis, diarrhea, and septicemia involving enteric pathogens in these patients.
• Determine the requirement for intravenous hyperalimentation in patients receiving amifostine, IDR, and ARA-C.

OUTLINE: This is a dose escalation study of idarubicin (IDR).

Patients receive amifostine IV over 15 minutes, followed 15-30 minutes later by chemotherapy. Idarubicin IV is administered over 15 minutes on days 1-3. Cytarabine is administered by continuous infusion on days 1-7. Patients may receive 1 additional course of treatment, if necessary.

Cohorts of 3-6 patients each are treated at each dose level of idarubicin. Dose escalation is discontinued when 2 or more patients experience dose limiting toxicity.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Newly diagnosed acute myeloid leukemia (AML)

• M0-M2, M4-M7
• Histologically proven by bone marrow aspirate and biopsy (requirement may be waived for patients with overt leukemia in the peripheral blood)
• M3 (acute promyelocytic leukemia) patients excluded unless already treated with trans retinoic acid
• Evaluable disease

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%
• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Not specified

Hepatic:

• SGOT/SGPT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Ejection fraction at least 50%
• Must be able to stop taking antihypertensive medication 24 hours prior to cytarabine administration

Other:

• No preexisting severe organ dysfunction
• No history of underlying medical or psychiatric illness that may impair the patient's ability to participate in the study
• Not pregnant or nursing
• Effective contraception required of fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior cytotoxic therapy for AML
• No prior amifostine
• At least 1 month since chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 1 month since radiotherapy

Surgery:

• Not specified