211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of radiation delivered via 211^At-BC8-B10
when combined with fludarabine phosphate (FLU) and 2 or 3 gray (Gy) total body irradiation
(TBI) as a preparative regimen for patients aged >= 18 with advanced acute myeloid leukemia
(AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

I. To determine disease response and duration of remission.

II. To determine the rates of engraftment and donor chimerism resulting from this combined
preparative regimen, and to correlate level of donor chimerism with amount of 211^At
administered.

OUTLINE: This is a dose-escalation study of 211^At-BC8-B10.

Patients receive 211^At-BC8-B10 intravenously (IV) over 6-8 hours on day -7 and fludarabine
phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and peripheral blood
stem cell (PBSC) transplant on day 0. Patients also receive cyclosporine orally (PO) or IV
every 12 hours on days -3 to 56 and then tapered to day 180, or continuing to day 96 and then
tapered to day 150. Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6
hours after PBSC infusion) every 12 hours on days 0-27, or every 8 hours on day 0 and then
reduced to every 12 hours on days 30-40. Patients with HLA-matched unrelated donors receive
sirolimus PO once daily (QD) on days -3 to 150 and then tapered to day 180.

After completion of study treatment, patients are followed up at 100 days and then 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

- 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

- Patients must have normal hepatic function (bilirubin, 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 have an HLA-matched related donor or an HLA-matched unrelated donor who
meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor
Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or
bone marrow donation, as follows:

- Related donor: related to the patient and genotypically or phenotypically
identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed
by high-resolution typing

- Unrelated donor:

- Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR

- Mismatched for a single allele without antigen mismatching at HLA-A, B, or C
as defined by high resolution typing but otherwise matched for HLA-A, B, C,
DRB1 and DQB1 by high resolution typing

- Donors are excluded when preexisting immunoreactivity is identified that
would jeopardize donor hematopoietic cell engraftment; the recommended
procedure for patients with 10 of 10 HLA allele level (phenotypic) match is
to obtain panel reactive antibody (PRA) screens to class I and class II
antigens for all patients before hematopoietic cell transplant (HCT); if the
PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic
cross matches should be obtained; the donor should be excluded if any of the
cytotoxic cross match assays are positive; for those patients with an HLA
Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross
matches should be obtained regardless of the PRA results; a positive
anti-donor cytotoxic crossmatch is an absolute donor exclusion

- Patient and donor pairs homozygous at a mismatched allele in the graft rejection
vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the
donor is A*0102, and this type of mismatch is not allowed

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 < 35%

- Corrected diffusing capacity of the lungs 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
positive [beta-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