A Phase I/II Study Evaluating Escalating Doses of 211At-labeled anti-CD45 MAb BC8-B10 (211At-BC8-B10) followed by Related Haplo-identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS).
Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:
?AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);
?AML or ALL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens);
?AML evolved from myelodysplastic or myeloproliferative syndromes;
?MDS expressed as refractory anemia with excess blasts (RAEB)
?Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria.
Patients not in remission must have CD45-expressing leukemic blasts. Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up >= 95% of nucleated cells in the marrow).
Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed).
Patients must have an estimated creatinine clearance greater than 50/ml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 days prior to registration.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
Eastern Cooperative Oncology Group (ECOG) = 70.
Patients must be free of uncontrolled infection.
Patients must not have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation.
Patients must have a related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches.
DONOR: Donors must meet HLA matching criteria as well as standard SCCA or NMDP or other donor center criteria for PBSC or bone marrow donation. Preference should be given to donors who are mismatched at the HLA-A, -B and -DRB1 loci.
Other eligibility criteria may apply.
Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects.
Left ventricular ejection fraction
Corrected diffusion capacity of the lung for carbon monoxide (DLCO)
Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease.
Patients who are known to be seropositive for human immunodeficiency virus (HIV).
Perceived inability to tolerate diagnostic or therapeutic procedures.
Active central nervous system (CNS) leukemia at time of treatment.
Women of childbearing potential who are pregnant (beta human chorionic gonadotropin [B-HCG]+) or breast feeding.
Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant.
Inability to understand or give an informed consent.
Allergy to murine-based monoclonal antibodies.
Known contraindications to radiotherapy.
Other exclusion criteria may apply.