211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome
211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome
This phase I/II trial studies the side effects and best dose of a radioactive agent linked to
 an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with
 high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't
 responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may
 interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total
 body irradiation before a stem cell transplant helps stop the growth of cells in the bone
 marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy
 stem cells from a donor are infused into the patient, they may help the patient's bone marrow
 make stem cells, red blood cells, white blood cells, and platelets. Sometimes the
 transplanted cells from a donor can attack the body's normal cells, called graft versus host
 disease. Giving cyclophosphamide, mycophenolate mofetil, and sirolimus after a transplant may
 stop this from happening.
OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody
 BC8-B10.

 PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10
 infusion over 6-8 hours 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. Patients also undergo TBI on
 day -1.

 TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on
 day 0.

 GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4,
 mycophenolate mofetil IV or PO three times daily (TID) on days 5-35, and tacrolimus IV over
 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per
 physician discretion. Patients 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, patients are followed up at day 100, and at 6, 9, 12,
 18, and 24 months.
Inclusion Criteria:

 -  Patients must have AML, ALL or high-risk MDS, or MPAL (also known as bipheontypic)
 meeting one of the following descriptions:

 -  AML, ALL, or MPAL in first remission with evidence of measurable residual disease
 (MRD) by flow cytometry;

 -  AML, ALL, or MPAL beyond first remission (i.e., having relapsed at least one time
 after achieving remission in response to a treatment regimen);

 -  AML, ALL, or MPAL 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 with prior non-myeloablative or reduced-intensity conditioning allogeneic-HCT
 must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6
 weeks at time of enrollment.

 -  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 Seattle Cancer Care
 Alliance (SCCA) 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. When pulmonary function tests (PFTs) cannot be
 obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used:
 Any patient with oxygen saturation on room air of < 89% during a 6MWT will be excluded

 -  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.

 -  Patients with prior myeloablative allogeneic-HCT.

 -  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.