NCT05662904

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

Genetic Ablation of CD33 in Hematopoietic Stem Cells to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients with Acute Myeloid Leukemia (AML)

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: German Cancer Research Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

CRISPR/Cas9-mediated inactivation of CD33 in hematopoietic stem cells (HSC) may broaden the therapeutic index of CD33-directed immunotherapy for patients with AML by rendering healthy hematopoietic stem and progenitor cells (HSPC) resistant to escalating doses and/or shorter dosing intervals of the CD33-specific antibody-drug conjugate (ADC) Gemtuzumab-ozogamicin (GO). In this proof of concept trial, we will develop a platform for genome editing of CD34+ HSC and demonstrate the feasibility, safety and efficacy of this approach for targeted therapy of AML. Upon implementation, the platform shall be used for innovative clinical trials in diverse types of cancer. Outside of leukemias, autologous HSC could be used to ease the procedure. 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. Upon HSC engraftment, patients will be treated with escalating doses of the anti-CD33 antibodydrug conjugate Gemtuzumab-Ozogamicin (GO). A conditioning regimen containing GO (d-14, d-11, d-8),Fludarabine 30 mg/m2 (d-6 to d-3) and Melphalan 140mg/m2 (d-2) is used prior to transplantation. The clinical trial will be conducted at two trial sites in the University Hospitals in Heidelberg and Dresden. 25 patients will be assessed for eligibility and 12 patients will be allocated into the trial.

Conditions

• Relapsed/Refractory Acute Myeloid Leukemia (AML)

Interventions

Type	Name	Description
BIOLOGICAL	Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion	CD33-deleted CD34+ hematopoietic stem cells derived from the initially matched family donor
DRUG	Gemtuzumab Ozogamicin	Intrapatient intra-individual dose escalation Level 0: GO day 1 Level 1: GO day 1, day 4 Level 2: GO day 1, day 4, day 7 with repetition after 21 to 28 days up to 84 days.

Timeline

• Start date: 2028-01-01
• Primary completion: 2029-01-01
• Completion: 2030-01-01
• First posted: 2022-12-23
• Last updated: 2025-03-14

Locations

2 sites across 1 country: Germany