211At-BC8-B10 and Donor Stem Cell Transplant in Treating Relapsed or Refractory AML, ALL, or Myelodysplastic Syndrome

OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody
BC8-B10.

PREPARATIVE REGIMEN: Participants receive astatine At 211 anti-CD45 monoclonal antibody
BC8-B10 infusion on day -8, fludarabine intravenously (IV) over 30 minutes on days -6 to -2,
and cyclophosphamide IV over 1 hour on days -6 and -5. Participants also undergo TBI on day
-1.

TRANSPLANT: Participants undergo PBSC or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Participants receive cyclophosphamide IV over 1-2 hours on days 3-4,
tacrolimus IV over 1-2 hours or orally (PO) on days 5-150 with a taper beginning on day 84,
mycophenolate mofetil IV or PO on days 5-35, and sirolimus PO daily on days 5-180 with taper
beginning on day 150. Participants also begin granulocyte colony-stimulating factor (G-CSF)
IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) >
1000/mm^3 X 3 days.

After completion of study treatment, participants are followed up at day 100, and at 6, 9,
12, 18, and 24 months.

Inclusion Criteria:

- 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.

- Bilirubin < 2 times the upper limit of normal.

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the
upper limit of normal.

- Eastern Cooperative Oncology Group (ECOG) < 2 or Karnofsky >= 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.

Exclusion Criteria:

- 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 < 45%.

- Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 35% or receiving
supplemental continuous oxygen.

- 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.