RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody in treating patients with myelodysplastic syndrome or relapsed or refractory acute myeloid leukemia or chronic myelogenous leukemia.

Condition	Treatment or Intervention	Phase
accelerated phase chronic myelogenous leukemia Previously Treated Myelodysplastic Syndrome recurrent adult acute myeloid leukemia de novo myelodysplastic syndrome refractory anemia with excess blasts in transformation refractory anemia with excess blasts refractory chronic myelogenous leukemia Chronic Myelomonocytic Leukemia blastic phase chronic myelogenous leukemia	Drug: monoclonal antibody HuG1-M195	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and toxicity of yttrium-90-labeled humanized monoclonal antibody M195 (90Y-MOAB HuM195) in patients with relapsed or refractory myeloid malignancies.

II. Determine the pharmacology and dosimetry of 90Y-MOAB HuM195.

III. Study the biological effects of 90Y-MOAB HuM195, including the ability to elicit human anti-human antibody responses and antileukemic responses.

PROTOCOL OUTLINE: This study seeks to estimate the maximum tolerated dose (MTD) of yttrium-90-labeled humanized monoclonal antibody M195 (90Y-MOAB HuM195).

All patients receive a single intravenous dose of 90Y-MOAB HuM195. Groups of 3 to 6 patients are treated at escalated doses of yttrium-90 until the MTD is determined.

Patients with active leukemia who exhibit at least a 50% clearing of marrow blasts after the first dose may receive a second dose after 4-8 weeks provided remaining blasts are CD33-positive, there is no evidence of human anti-human antibody response, and any toxicity has resolved.

All patients are followed monthly for 4 months after treatment.

PROJECTED ACCRUAL: Up to 24 patients will be treated. The study is expected to require 12-18 months to complete.

Ages Eligible for Study:  16 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Pathologically confirmed myeloid malignancies as follows: Acute myelogenous leukemia that is relapsed or refractory after at least 2 courses of standard induction chemotherapy; Accelerated or myeloblastic chronic myelogenous leukemia; Refractory anemia with excess blasts (RAEB); RAEB in transformation; Chronic myelomonocytic leukemia
• More than 25% of bone marrow blasts positive for the CD33 antigen
• Clear signs of active leukemia following recovery from prior therapy required
• No rapidly accelerating blast count
• No clinically unstable disease
• No active CNS leukemia

--Prior/Concurrent Therapy--

• Recovered from prior therapy
• Biologic therapy: No detectable antibodies to M195 from prior monoclonal antibody M195 or HuM195
• Chemotherapy: At least 2 days since hydroxyurea; At least 3 weeks since other chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 3 weeks since radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: Over 16
• Performance status: Karnofsky 60%-100%
• Life expectancy: At least 6 weeks
• Hematopoietic: Not specified
• Hepatic: Bilirubin less than 2.5 mg/dL; AST less than 3 times normal; Alkaline phosphatase less than 3 times normal
• Renal: Creatinine less than 2.0 mg/dL
• Cardiovascular: No NYHA class III/IV status
• Pulmonary: No clinically significant pulmonary disease
• Other: No serious infection uncontrolled by antibiotics; No pregnant or nursing women; Negative pregnancy test required of fertile women

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Joseph G. Jurcic,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000065213; MSKCC-96010; NCI-H96-1100
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002890
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08