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Relapsed/Refractory Acute Myeloid Leukemia (AML)Phase 1GALAXY33NCT05662904

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

A Phase 1 study testing Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion and Gemtuzumab Ozogamicin in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by German Cancer Research Center at 2 sites in Germany.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion and Gemtuzumab Ozogamicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesGermany
Study dates
Jan 2028to Jan 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

Germany2 sites

  • University Hospital Dresden, Department of Medicine I

    Dresden, 01307

    Martin Bornhäuser, Prof. Dr. med.

  • University Hospital Heidelberg, Internal Medicine V

    Heidelberg, 69120

    Tim Sauer, Dr. med.

Other trials in Germany

About this study

Official title: Genetic Ablation of CD33 in Hematopoietic Stem Cells to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients with Acute Myeloid Leukemia (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.

Read the 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.

Being tested
Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion, Gemtuzumab Ozogamicin
Keywords
AML, allogeneic stem cell transplantation, gene editing, chemotherapy resistance
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletionBiological

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

  • Gemtuzumab OzogamicinDrug

    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.

Study groups in NCT05662904
Study groupRoleWhat they receive
Donor-derived CD33-deleted CD34+ HSC combined with Gemtuzumab-Ozogamicin (GO)ExperimentalPatients 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.
Receives: Biological: Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion; Drug: Gemtuzumab Ozogamicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. engraftement of gene edited CD34+HSC

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

    Measured: on day 28

  2. dose-limiting toxicity

    dose-limiting toxicity (DLT) of Gemtuzumab-Ozogamicin

    Measured: until EOS (day 90)

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

    frequency and grade of AEs with gene-edited HSC transplantation

    Measured: until EOS (day 90)

Secondary outcomes (6)

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

    overall response rate (ORR), complete response (CR), partial response (PR)) at day 90 (EOS) after last GO application)

    Measured: until EOS (day 90)

  2. Time to response

    Time to response (at least partial response) after the last GO application

    Measured: until EOS (day 90)

  3. Overall response

    Duration of overall response (DOR) after the last GO application

    Measured: until EOS (day 90)

  4. Progression-free survival

    Progression-free survival (PFS) after the last GO application

    Measured: until EOS (day 90)

  5. Overall survival

    Overall survival (OS) after the last GO application

    Measured: until EOS (day 90)

  6. Number of circulating gene edited cells

    Number of circulating gene edited cells in the bone marrow and peripheral blood as determined by flow cytometry

    Measured: at screening and days 14, 28, 56, 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2022
  2. Study startJan 2028 (estimated)
  3. Primary completionJan 2029 (estimated)
  4. Study completionJan 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05662904
Sponsor's protocol ID
2022-002
Acronym
GALAXY33
Status last verified
Mar 2025
First submitted
6 Dec 2022
Last updated
14 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion and Gemtuzumab Ozogamicin in people with Relapsed/Refractory Acute Myeloid Leukemia (AML), run by German Cancer Research Center at 2 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 14 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tim Sauer, Dr. med. (+49 6221 56 38010, tim.sauer@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

engraftement of gene edited CD34+HSC (time frame: on day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05662904.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2025.

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