Genetic Ablation of CD33 in HSC to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients With AML (GALAXY33)

Key Inclusion Criteria: confirmed AML according to the WHO classification relapsed disease after allo-SCT from an HLA-identical family donor (≥ 2 months after allo-SCT at time of inclusion) ≤ 29% of bone marrow blasts as detected by cytomorphology or immunohistochemistry age ≥ 18 years confirmed CD33 expression on leukemic blasts at current relapse (as detected by flow cytometry) adequate organ function: Renal function defined as: serum creatinine of ≤ 2x ULN or eGFR ≥ 30 mL/min/1.73 m2 Liver function defined as: ALT ≤ 3 times the ULN for the respective age Bilirubin ≤ 2.0 mg/dl with the exception of patients with hyperbilirubinemia explained by Gilbert-Meulengracht syndrome (may be included if total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) or extrahepatic disease (e.g. chronic hemolytic anemia) Minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation > 90% on room air Hemodynamic stability and LVEF ≥ 40% as confirmed by echocardiogram Absolute lymphocyte count (ALC) ≥ 100/mm3 Key Exclusion Criteria: ECOG performance status >2 Confirmed CNS involvement Acute or chronic Graft versus Host disease (GvHD) Availability of other curative standard treatment options Prior treatment with GO Prior hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) Uncontrolled active hepatitis B or C HIV-positivity Uncontrolled bacterial, viral or fungal infection Participation in another clinical trial at the time of screening Organ dysfunction (liver, kidney, lung, heart) that is a contraindication for conditioning therapy Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure NYHA III-IV, uncontrolled diabetes mellitus, uncontrolled hyperlipidemia) Unstable angina and/or myocardial infarction within 3 months prior to screening Pregnant or nursing (lactating) women