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

NCT05662904 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2022-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia (AML)

Keywords

AML; allogeneic stem cell transplantation; gene editing; chemotherapy resistance

Outcome Measures

Primary Outcomes (3)

• engraftement of gene edited CD34+HSC

  successful engraftement of gene edited CD34+HSC in the bone marrow

  on day 28

• dose-limiting toxicity

  dose-limiting toxicity (DLT) of Gemtuzumab-Ozogamicin

  until EOS (day 90)

• toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  frequency and grade of AEs with gene-edited HSC transplantation

  until EOS (day 90)

Secondary Outcomes (6)

• Anti-tumor efficacy of study treatment in patients with dCD33+ relapsed AML after allo-SCT

  until EOS (day 90)

• Time to response

  until EOS (day 90)

• Overall response

  until EOS (day 90)

• Progression-free survival

  until EOS (day 90)

• Overall survival

  until EOS (day 90)

Study Arms (1)

Donor-derived CD33-deleted CD34+ HSC combined with Gemtuzumab-Ozogamicin (GO)

EXPERIMENTAL

Patients 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 antibodydrugconjugate 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.

Biological: Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion; Drug: Gemtuzumab Ozogamicin

Interventions

Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion BIOLOGICAL

CD33-deleted CD34+ hematopoietic stem cells derived from the initially matched family donor

Donor-derived CD33-deleted CD34+ HSC combined with Gemtuzumab-Ozogamicin (GO)

Gemtuzumab Ozogamicin DRUG

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.

Donor-derived CD33-deleted CD34+ HSC combined with Gemtuzumab-Ozogamicin (GO)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• confirmed AML according to the WHO classification
• ≤ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• German Cancer Research Center: lead
• University Hospital Heidelberg: collaborator
• University Hospital Dresden: collaborator

Study Sites (2)

University Hospital Dresden, Department of Medicine I

Dresden, 01307, Germany

Location

University Hospital Heidelberg, Internal Medicine V

Heidelberg, 69120, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tim Sauer, Dr. med.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tim Sauer, Dr. med.

CONTACT

+49 6221 56 38010; tim.sauer@med.uni-heidelberg.de

Carsten Müller-Tidow, Prof. Dr. med.

CONTACT

carsten.mueller-tidow@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 23, 2022
• Study Start (Estimated): January 1, 2028
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)