Radiolabeled Monoclonal Antibody Therapy and Etoposide Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Myelodysplastic Syndrome or Refractory Leukemia

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 humanized monoclonal antibody M195 when combined with etoposide as a preparative regimen for autologous peripheral blood stem cell transplantation in patients with advanced myelodysplastic syndrome or refractory leukemia.
• Determine the qualitative toxicities associated with this regimen in this patient population.
• Assess preliminary information on engraftment following this conditioning regimen in these patients.

OUTLINE: This is a dose escalation study of yttrium Y 90 humanized monoclonal antibody M195 (Y90 MOAB M195).

Patients receive Y90 MOAB M195 IV over 40 minutes once between days -12 to -9 and etoposide IV over several hours on day -3. Peripheral blood stem cells or bone marrow are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 1 until hematopoietic recovery.

Cohorts of 3-6 patients receive escalating doses of Y90 MOAB M195 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.

Patients are followed between days 10 and 14 and then monthly for 6 months.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 12 months.

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

• Acute myeloid leukemia
• Accelerated/blastic phase of a myeloproliferative disorder (i.e., greater than 10% blasts in bone marrow or presence of extramedullary disease)
• Myelodysplastic syndrome
• Acute lymphocytic leukemia with expression of CD33

• Greater than 20% blast population
• No evidence of CNS disease
• Relapsed after previously achieving complete remission
• Must have previously had peripheral blood stem cells or bone marrow cells harvested and cryopreserved while in remission
• Greater than 25% of bone marrow blasts must be CD33 positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• LVEF greater than 50% by ECG or MUGA
• No history of cardiomyopathy or symptomatic congestive heart failure

Pulmonary:

• DLCO at least 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• HIV negative
• No other concurrent active malignancy
• No known sensitivity to E. coli derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified