Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of radiation delivered via PRIT using BC8-SA
(BC8 antibody-streptavidin conjugate) when combined with fludarabine (FLU) (fludarabine
phosphate), 2 Gy total body irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil
(MMF), and allogeneic hematopoietic cell transplant (HCT) in patients who have advanced
acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high risk
myelodysplastic syndromes (MDS).

SECONDARY OBJECTIVES:

I. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting
from this combined preparative regimen.

II. To estimate rates of disease relapse, acute graft-versus-host disease (GvHD), and
day-100 disease-free survival in patients receiving PRIT using BC8-SA combined with FLU, 2
Gy TBI, CSP, MMF, and allogeneic HCT.

III. To assess biodistribution, serum half-life, urinary excretion, tissue localization, and
clearance of BC8-SA conjugate and DOTA-biotin.

IV. To assess the feasibility of yttrium y 90 (90Y)-DOTA-biotin to bind to BC8-SA conjugate
localized to hematolymphoid tissues.

OUTLINE:

Patients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate
intravenously (IV) on day -22 and indium In 111(111In)-DOTA-biotin IV on day -20, followed
by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12.
Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then
peripheral blood stem cell transplantation on day 0. Patients with matched related donors
receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil
orally (PO) twice daily (BID) on days 0-27. Patients with matched unrelated donors receive
cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO thrice
daily (TID) on days 0-40 and taper to day 96.

After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24
months, and then annually thereafter.

Inclusion Criteria:

- Patients with advanced AML or ALL defined as beyond first remission, primary
refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes;
or patients with MDS expressed as refractory anemia with excess blasts (RAEB),
refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed
sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)

- 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
nonmalignant 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

- Bilirubin < 2 times the upper limit of normal

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

- Karnofsky score >= 70 or Eastern Cooperative Oncology Group (ECOG) =< 2

- Patients must have an expected survival of > 60 days and must be free of active
infection

- Patients must have an human leukocyte antigen (HLA)-identical sibling 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) donation; related donors should be matched by
molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1
according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice
Guidelines and to the allele level at DQB1; unrelated donors should be identified
using matching criteria that follows the FHCRC standard practice guidelines limiting
the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1
(Grade 1), and accepting up to one allele mismatch as per standard practice grade 2.1
for HLA-A, B, or C; PBSC is the only permitted stem cell source

- DONOR: Donors must meet HLA matching criteria as well as standard SCCA and/or NMDP,
or other donor center criteria for PBSC donation

Exclusion Criteria:

- Circulating human anti-mouse antibody (HAMA) or human anti-streptavidin antibody
(HASA)

- Prior radiation to maximally tolerated levels to any critical normal organ

- Patients may not have symptomatic coronary artery disease and may not be on cardiac
medications for anti-arrhythmic or inotropic effects

- Patients with the following organ dysfunction:

- Left ventricular ejection fraction < 35%

- Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 35% and/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 seropositive for human immunodeficiency virus (HIV)

- Perceived inability to tolerate diagnostic or therapeutic procedures, particularly
treatment in radiation isolation

- Active central nervous system (CNS) leukemia

- 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

- Patients may not use vitamin supplements containing biotin from the time of 1 week
prior to treatment until 1 week after completion of treatment with all PRIT
components

- Inability to understand or give an informed consent