Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS

Inclusion Criteria

• Must be ≥18 and ≤70 years of age.
• Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse:
• BM in morphological remission (<5% blasts) with adverse-risk disease related genetics at presentation (according to European Leukemia-Net guidelines [ELN, Döhner 2017]), or
• Intermediate risk genetics in morphologic remission (<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or
• BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM Blast count >10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or
• Any patient in second or greater remission.
• Patients with MDS must have all of the following:
• Previous or current IPSS-R score of High or Very High risk; AND
• Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria (Khoury 2022)
• AML sample from the patient must have evidence of CD33 expression (>0%)
• Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen.
• Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1.
• Must have adequate performance status and organ function as defined below:
• Performance Status: Karnofsky score of ≥70.
• Cardiac: left ventricular ejection fraction (LVEF) ≥50%
• Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%.
• Renal: estimated glomerular filtration rate (GFR) >60 mL/min
• Hepatic: total bilirubin <1.5 × ULN, or if ≥1.5 × ULN direct bilirubin <ULN and ALT/AST <1.5 × ULN (per institutional criteria).

Exclusion Criteria

• Prior autologous or allogeneic stem cell transplantation.
• Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia.
• Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months.
• Active central nervous system (CNS) leukemia.
• Patients diagnosed with Gilbert's syndrome.
• Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.