Gemtuzumab Ozogamicin and High-Dose Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

OBJECTIVES:

• Determine the response rate in patients with relapsed or refractory acute myeloid leukemia treated with gemtuzumab ozogamicin (CMA-676) and high-dose cytarabine.
• Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemtuzumab ozogamicin (CMA-676) (phase I closed to accrual effective 08/25/2003). Patients are stratified according to disease status (refractory vs relapsed).

• Phase I (closed to accrual effective 08/25/2003): Patients are enrolled in one of four cohorts.

• Cohort I (closed to accrual as of 10/1/02): Patients receive CMA-676 at the first dose level IV over 2 hours on days 1 and 8.
• Cohort IA (open to accrual as of 10/15/02): Patients receive high-dose cytarabine (HD-ARA-C) IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7.
• Cohort II: Patients receive HD-ARA-C as in cohort IA and CMA-676 at the first dose level IV over 2 hours on days 7 and 14.
• Cohort IV: Patients receive CMA-676 at the second dose level and HD-ARA-C as in cohort II.

Dose escalation stops if at least 3 of 9 patients experience dose-limiting toxicity.

• Phase II: Patients receive HD-ARA-C IV over 3 hours on days 1-5 and CMA-676 IV over 2 hours on day 7 (one course).

Patients are followed at 1 month, monthly for 6 months, every 3 months for 2 years, and then annually for 10 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study and a total of 37 patients will be accrued for phase II of the study within 2 years. (Phase I closed to accrual effective 08/25/2003).

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

• Primary refractory acute myeloid leukemia (AML)

• More than 10% blasts in the bone marrow or blood after recovery from 2 courses of standard cytarabine- and anthracycline-based induction chemotherapy
• No prior remission
• Relapsed AML

• More than 10% blasts in the bone marrow or blood after documented remission
• Prior remission lasted more than 30 days
• No prior treatment for current relapse
• CD33 expression on at least 20% of leukemia blast cells at initial diagnosis for primary refractory patients or at the time of relapse for all other patients
• No active CNS involvement

PATIENT CHARACTERISTICS:

Age:

• 17 and over

Performance status:

• 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• WBC less than 30,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• No veno-occlusive disease of the liver
• No chronic liver disease unless due to AML

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 6 months since prior stem cell transplantation

Chemotherapy:

• See Disease Characteristics
• Prior etoposide and/or thioguanine during remission induction allowed
• Prior hydroxyurea for control of AML allowed
• At least 24 hours since prior hydroxyurea
• At least 3 months since prior high-dose cytarabine (greater than 2 g/m^2/dose)-containing regimen
• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent steroids for adrenal failure, hypersensitivity reactions, or septic shock allowed
• Concurrent ophthalmic corticosteroids allowed
• Concurrent hormones for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) allowed

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• More than 2 months since prior cytotoxic therapy