Chemotherapy Plus Monoclonal Antibody in Treating Patients With Acute Promyelocytic Leukemia

OBJECTIVES:

• Determine the disease-free and overall survival of patients with acute promyelocytic leukemia in clinical complete remission following tretinoin-based induction therapy treated with monoclonal antibody HuG1-M195, arsenic trioxide, idarubicin, and tretinoin.
• Determine the rate of molecular complete remission in patients treated with this regimen.
• Determine the toxicity of this regimen in this patient population.
• Determine the number and length of hospitalizations of patients treated with this regimen.

OUTLINE: Patients receive monoclonal antibody HuG1-M195 (MOAB HuM195) IV over 40-60 minutes twice weekly for 3 weeks. Approximately 2-4 weeks after completion of MOAB HuM195, patients receive arsenic trioxide IV over 1-4 hours daily for a total of 25 days with no more than 5 days between doses.

Beginning approximately 4-6 weeks after completion of arsenic trioxide, patients receive idarubicin IV daily on days 1-3 or 1-4 and filgrastim (G-CSF) subcutaneously daily beginning on day 5 or 6 and continuing until blood counts recover. Treatment repeats every 4 weeks for patients who remain RT-PCR positive or are newly converted to RT-PCR negative (molecular complete remission) following a prior course of idarubicin for a maximum of 3 courses. Patients who remain RT-PCR positive following course 3 of idarubicin receive no further treatment on study.

Beginning 3 months after completion of idarubicin, patients in molecular complete remission receive oral tretinoin daily for 14 days. Treatment repeats every 3 months for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly.

PROJECTED ACCRUAL: Approximately 35 patients will be accrued for this study within 2-3 years.

DISEASE CHARACTERISTICS:

• Diagnosis of acute promyelocytic leukemia by positive RT-PCR assay for PML/RAR-alfa rearrangement or a t(15;17) karyotype

• Achieved clinical complete remission within the past 1-2 months
• Prior induction therapy must have contained tretinoin
• No other acute myeloid leukemia diagnosis

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminases no greater than 3 times upper limit of normal

Renal:

• Creatinine less than 2 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Ejection fraction normal or greater than 50% by echocardiogram or MUGA

Other:

• No other concurrent active malignancy
• No other serious or life-threatening condition that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 1 week since prior retinoids

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No prior postremission therapy of any form