Radiolabeled Monoclonal Antibody, Cyclophosphamide, and Total Body Irradiation Followed By Donor Stem Cell Transplantation in Treating Patients With Advanced Acute Myeloid Leukemia

OBJECTIVES:

• Determine the efficacy, in terms of overall survival and disease-free survival, and toxicity of cyclophosphamide and total body irradiation in patients with acute myeloid leukemia beyond first remission receiving HLA-matched related or unrelated hematopoietic stem cell transplantation.
• Determine the maximum tolerated dose (MTD) of iodine I 131 monoclonal antibody BC8 (I131 MOAB BC8) in these patients.
• Estimate the MTD of radiation delivered by I 131 MOAB BC8 to marrow of these patients and assess the effects on growth of marrow stroma in vitro.

OUTLINE: This is radiation dose-escalation study. Patients are stratified according to available donor (related vs unrelated).

Patients receive a biodistribution dose of iodine I 131 monoclonal antibody BC8 (I131 MOAB BC8) IV, then a therapeutic dose of I131 MOAB BC8 IV 6-14 days later (day -12). Patients undergo total body irradiation twice daily on days -6 to -4. Patients receive cyclophosphamide IV on days -3 and -2. Bone marrow cells (or peripheral blood stem cells) are infused on day 0.

Patients with CNS leukemic involvement receive intrathecal methotrexate twice before the transplantation then every other week for 8 weeks beginning on day 32. These patients also receive cranial irradiation beginning on day 32.

Cohorts of 4 patients each receive escalating doses of iodine I 131 attached to a standard dose of monoclonal antibody BC8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the radiation dose preceding that at which 2 of up to 6 patients experience graft failure.

Patients are followed at 6, 9, and 12 months, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Acute myeloid leukemia (AML) beyond first remission OR with primary refractory disease
• AML that has transformed from myelodysplastic syndromes, if induction chemotherapy not recommended
• Documented CD45 expression in patients with relapsed disease

• Not needed for patients in remission
• Circulating blast count less than 10,000/mm^3 (may be controlled with hydroxyurea or similar agent)

PATIENT CHARACTERISTICS:

Age

• 2 to 55

Performance status

• Not specified

Life expectancy

• More than 60 days

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin less than 1.5 mg/dL (unless bilirubin is determined by the gastroenterology service to be predominantly unconjugated [indirect] as the result of possible hemolysis)
• AST less than 1.5 times upper limit of normal (ULN)

Renal

• Creatinine less than 2.0 mg/dL OR less than 1.5 times ULN for age

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No major infection
• No circulating antibodies to mouse immunoglobulins
• HIV negative
• Able to tolerate diagnostic or therapeutic procedures (e.g., radiation isolation)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• No radiotherapy to maximum tolerated levels to any normal organ

Surgery

• Not specified