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

• Status: Not yet recruiting
• Trial end date: 2025-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German Cancer Research Center
• Collaborators: University Hospital Dresden; University Hospital Heidelberg
• Treatments: Gemtuzumab

Criteria

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