Allogeneic Stem Cell Transplantation Followed By Targeted Immune Therapy In Average Risk Leukemia

Gemtuzumab Ozogamicin (CMA-676) is a chemotherapeutic agent consisting of a recombinant
humanized anti-CD33 antibody conjugated with calicheamicin, a highly potent cytotoxic
antitumor antibiotic. The antibody portion of Gemtuzumab binds specifically to the CD33
antigen, a sialic acid-dependent adhesion protein expressed on the surface of leukemic
blasts, normal and leukemic myeloid colony-forming cells, including leukemic clonogenic
precursors, but excluding pluripotent hematopoietic stem cells and nonhematopoietic cells.
This results in formation of a complex that is internalized, upon which the calicheamicin
derivative is released within the lysosomes of the myeloid cell. The free calicheamicin
derivative then binds to deoxyribonucleic acid (DNA), resulting in DNA double strand breaks
and consequential cell death. Over 80% of AML patients possess myeloid blast cells with CD33
surface antigen expression.

Inclusion Criteria:

Disease Status

- AML 1st CR with a matched family donor (excluding Downs Syndrome, APL, poor
cytogenetics [12p, 5q, -7 and FLT3 mutations or duplication t(9;11) and others]) and
patients consented to and registered on an upfront AML COG study with a matched
family donor)

- AML 1st CR [excluding Downs Syndrome, APL, and chromosome translocation (8;21) or
inversion (16) or poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication
t(9;11) and others)] with unrelated donor

- AML 2nd CR

- Myelodysplastic Syndrome (MDS) and ≤ 5% bone marrow myeloblasts at diagnosis (de novo
patients only)

- Juvenile Myelomonocytic Leukemia (JMML) and ≤ 5% bone marrow myeloblasts at diagnosis

In regards to disease immunophenotype, disease must express a minimum of ≥10% CD33
positivity for patients with AML

Organ Function:

Patients must have adequate organ function as defined below:

Adequate renal function defined as:

- Serum creatinine < 1.5 x normal, or

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) 40 ml/min/m2 or
> 60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal
range

Adequate liver function defined as total bilirubin 2.0 x upper limit of normal (ULN), or
serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase (AST)) or serum
glutamic-pyruvic transaminase (SGPT)(alanine aminotransferase (ALT)) < 5.0 xULN

Adequate cardiac function defined as:

- Shortening fraction of ≥ 25% by echocardiogram, or

- Ejection fraction of ≥ 45% by radionuclide angiogram or echocardiogram

Adequate pulmonary function defined as:

- Diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 40% by pulmonary function
tests (PFT) (Uncorrected)

- For children who are uncooperative, no evidence of dyspnea at rest, no exercise
intolerance, and a pulse oximetry > 94% on room air

Exclusion Criteria:

- Patients with active central nervous system (CNS) AML/JMML disease at time of
preparative regimen

- Secondary MDS

- Poor cytogenetics (12p, 5q, -7, FLT3 mutation or duplication)

- Female patients who are pregnant (positive human chorionic gonadotropin(hCG))

- Karnofsky <70% or Lansky <50% if 10 years or less

- Age >30 years

- Seropositive for Human Immunodeficiency Virus (HIV)

- Patients consented to and registered on an upfront Children's Oncology Group (COG)
AML study with a matched family donor