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

Korábbi kezelés

• Prior treatment with GO
• Prior hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)
• 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

Más betegség

• Acute or chronic Graft versus Host disease (GvHD)
• Uncontrolled active hepatitis B or C
• HIV-positivity
• Uncontrolled bacterial, viral or fungal infection
• Organ dysfunction (liver, kidney, lung, heart) that is a contraindication for conditioning therapy

Egyéb

• ECOG performance status >2
• Confirmed CNS involvement
• Availability of other curative standard treatment options
• Participation in another clinical trial at the time of screening
• Pregnant or nursing (lactating) women

• 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