Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

PRIMARY OBJECTIVES:

I. To evaluate the maximum tolerated dose (MTD) and the transplant-related mortality (TRM)
and toxicity of delivering 131I-BC8 (iodine I 131 monoclonal antibody BC8) (anti-cluster of
differentiation [CD]45 antibody) at a starting dose of 22 Gy to the normal organ receiving
the highest dose in combination with the non-myeloablative regimen of fludarabine
(fludarabine phosphate) (FLU), 2 Gy total body irradiation (TBI), cyclosporine (CSP),
mycophenolate mofetil (MMF), and human leukocyte antigen (HLA)-matched related or unrelated
allogeneic hematopoietic stem cell transplant (HSCT) in patients 16 to 50 years old who have
advanced acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS).

II. To estimate rates of 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.

III. To determine rates of disease relapse, graft vs. host disease, and 2-year disease-free
survival in patients receiving 131I-BC8 antibody combined with FLU, 2 Gy TBI, CSP, MMF, and
HLA-matched related or unrelated allogeneic HSCT.

OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody BC8.

RADIOIMMUNOTHERAPY: Patients receive therapeutic iodine I 131 monoclonal antibody BC8
intravenously (IV) on day -12.

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on
day 0.

TRANSPLANTATION: After completion of TBI, patients undergo allogeneic peripheral blood stem
cell (PBSC) transplant on day 0.

IMMUNOSUPPRESSION: Patients with a matched related donor receive cyclosporine IV or orally
(PO) twice daily (BID) on days -3 to 56 followed by a taper to day 180 in the absence of
graft-versus-host disease. Beginning 4-6 hours after PBSC transplant, these patients also
receive mycophenolate mofetil PO BID on days 0 to 27. Patients with a matched unrelated donor
receive cyclosporine IV or PO BID on days -3 to 100 followed by a taper to day 180. Beginning
4-6 hours after PBSC transplant, these patients also receive mycophenolate mofetil PO thrice
daily (TID) on days 0 to 40 followed by a 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 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 anemia
with excess blasts in transformation (RAEBT), 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 or myelodysplastic
cells; 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 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 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 developmentally regulated RNA binding protein 1
(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

- 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 antibody against mouse immunoglobulin (human anti-mouse antibody [HAMA])

- Prior radiation to maximally tolerated levels to any normal organ

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

- Inability to understand or give an informed consent

- Patients who are seropositive for human immunodeficiency virus (HIV)

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

- Patients who have previously undergone autologous or allogeneic HSCT