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

The study "GALAXY33" is an open-label, prospective, nonrandomized, one arm phase I clinical trial in which patients with relapsed AML after allogeneic hematopoietic stem cell transplantation will be transplanted with CD33-deleted CD34+ HSC derived from the initially matched family donor.

Key Inclusion Criteria:confirmed AML according to the WHO classificationrelapsed 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 immunohistochemistryage ≥ 18 yearsconfirmed 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 m2Liver function defined as:ALT ≤ 3 times the ULN for the respective ageBilirubin ≤ 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 airHemodynamic stability and LVEF ≥ 40% as confirmed by echocardiogramAbsolute lymphocyte count (ALC) ≥ 100/mm3Key Exclusion Criteria:ECOG performance status >2Confirmed CNS involvementAcute or chronic Graft versus Host disease (GvHD)Availability of other curative standard treatment optionsPrior treatment with GOPrior hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)Uncontrolled active hepatitis B or CHIV-positivityUncontrolled bacterial, viral or fungal infectionParticipation in another clinical trial at the time of screeningOrgan dysfunction (liver, kidney, lung, heart) that is a contraindication for conditioning therapySevere 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 screeningPregnant or nursing (lactating) women