Yttrium-90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk AML, ALL, or MDS

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-DOTA-BC8
(90Y-BC8) when combined with FLU and 2 Gy TBI as a preparative regimen for patients aged >=
18 with advanced AML, ALL, and high-risk 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 estimated radiation doses
delivered to hematopoietic tissues via antibody.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on approximately day -12 and
FLU intravenously (IV) over 30 minutes on days -4 to -2.

TRANSPLANTATION: Patients undergo TBI followed by allogeneic PBSC or bone marrow transplant
on day 0.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil orally (PO)
or IV every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days
0-40 with taper to day 96 (for patients with unrelated donors). Patients also receive
cyclosporine PO or IV every 12 hours on days -3 to 56 (for patients with related donors) or
100 (for patients with unrelated donors) with taper to day 180.

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

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; or

- MDS expressed as refractory anemia with excess blasts (RAEB) or 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
(serum creatinine value must be within 28 days prior to registration)

- Bilirubin < 2 times the upper limit of normal

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

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

- 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 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

- Doors are excluded when preexisting immunoreactivity is identified that
would jeopardize donor hematopoietic cell engraftment; this determination is
based on the standard practice of the individual institution; 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 and 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

- DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow
Donor Program (NMDP) or other donor center criteria for PBSC or bone marrow donation

Exclusion Criteria:

- Circulating human anti-mouse antibody (HAMA)

- Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy
prior radiation to large areas of the bone marrow (e.g., external radiation therapy to
whole pelvis)

- 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 diffusion lung capacity of 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 [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