S0301 Cyclosporine, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

OBJECTIVES:

• Determine the safety and efficacy of cyclosporine, daunorubicin, and cytarabine in older patients with previously untreated acute myeloid leukemia.
• Determine the frequency and severity of toxic effects of this regimen in these patients.
• Determine, preliminarily, the frequency and prognostic significance of functional and phenotypic P-glycoprotein expression and cytogenetics in patients treated with this regimen.
• Determine, preliminarily, the pharmacokinetic characteristics of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive cyclosporine IV and daunorubicin IV continuously on days 1-3 and cytarabine IV continuously on days 1-7. Patients who achieve complete response (CR) after chemotherapy receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously beginning on day 15 or 20 and continuing until blood counts recover. Patients who maintain CR after 2 courses of induction therapy proceed to consolidation therapy.
• Consolidation therapy: Patients receive treatment as in induction therapy with cyclosporine and daunorubicin on days 1-2 and cytarabine on days 1-5. Patients achieving CR receive an additional course of chemotherapy beginning at least 14 days after completion of the first course of cytarabine.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 25-64 patients will be accrued for this study within 13 months.

DISEASE CHARACTERISTICS:

• Morphologically confirmed acute myeloid leukemia (AML)

• Differential diagnosis of AML based on FAB classification system

• M0-M7 (No M3)
• No blastic transformation of chronic myelogenous leukemia
• Must be currently registered on protocols SWOG-9007 and SWOG-S9910

PATIENT CHARACTERISTICS:

Age

• 56 and over

Performance status

• Zubrod 0-3 (for patients 56 to 60 years of age) OR
• Zubrod 0-2 (for patients 61 to 70 years of age) OR
• Zubrod 0-1 (for patients 71 years of age and over)

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN) unless elevated unconjugated hyperbilirubinemia is secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction
• AST and/or ALT no greater than 4 times ULN

Renal

• Creatinine no greater than 1.5 times ULN AND/OR
• Creatinine clearance greater than 40 mL/min

Cardiovascular

• Left ventricular function normal
• Ejection fraction at least 50% by MUGA or echocardiogram
• No unstable cardiac arrhythmias
• No unstable angina

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent pegfilgrastim

Chemotherapy

• At least 30 days since prior low-dose cytarabine (less than 100 mg/m^2/day) for myelodysplastic syndromes and recovered
• Prior hydroxyurea to control high cell counts allowed
• No prior systemic chemotherapy for acute leukemia
• Concurrent single-dose intrathecal chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified