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

Genetic Ablation of CD33 in Hematopoietic Stem Cells for AML

NCT: NCT05662904 · Status: NOT YET RECRUITING · Phase: Phase 1 · Sponsor: German Cancer Research Center · Started: 2028-01 · Est. Completion: 2030-01

Plain English Summary

Genetic Ablation of CD33 in HSC to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients with AML is a Phase 1 clinical trial sponsored by German Cancer Research Center studying Relapsed/Refractory Acute Myeloid Leukemia (AML). Tests a new method to remove CD33 from stem cells to improve CD33-directed immunotherapy for AML. For patients who have relapsed AML after a stem cell transplant from a family donor. Participation involves receiving edited stem cells and monitoring for side effects and response to treatment. Alternative treatments include standard chemotherapy and other immunotherapies. The trial aims to enroll 12 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if you have relapsed AML after a stem cell transplant from a family donor, are 18 years or older, and have CD33 on your leukemia cells. Not eligible if you have severe organ problems, active infections, or other serious health issues. This trial is studying Relapsed/Refractory Acute Myeloid Leukemia (AML), so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures focus on the success of the stem cell transplant and the safety of the treatment. The specific primary outcome measures are: engraftement of gene edited CD34+HSC (on day 28); dose-limiting toxicity (until EOS (day 90)); toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) (until EOS (day 90)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial aims to fill a gap in treatment options for relapsed AML by improving the effectiveness of existing immunotherapies. This research targets Relapsed/Refractory Acute Myeloid Leukemia (AML), where improved treatment options are needed.

Investor Insight

The market for AML treatments is large, with limited options for relapsed patients, making this trial potentially significant. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you have relapsed AML and have had a stem cell transplant from a family donor. Participation involves receiving edited stem cells and regular check-ups to monitor your health. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

  • Study Type: INTERVENTIONAL
  • Allocation: NA
  • Model: SINGLE_GROUP
  • Masking: NONE
  • Enrollment: 12 participants

Interventions

  • 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.

Primary Outcomes

  • engraftement of gene edited CD34+HSC (on day 28)
  • dose-limiting toxicity (until EOS (day 90))
  • toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) (until EOS (day 90))

Secondary Outcomes

  • 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))

Full Eligibility 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

Trial Locations

  • University Hospital Dresden, Department of Medicine I, Dresden, Germany
  • University Hospital Heidelberg, Internal Medicine V, Heidelberg, Germany

Frequently Asked Questions

What is clinical trial NCT05662904?

NCT05662904 is a Phase 1 INTERVENTIONAL study titled "Genetic Ablation of CD33 in HSC to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients with AML." It is currently not yet recruiting and is sponsored by German Cancer Research Center. The trial targets enrollment of 12 participants.

What conditions does NCT05662904 study?

This trial investigates treatments for Relapsed/Refractory Acute Myeloid Leukemia (AML). The primary condition under study is Relapsed/Refractory Acute Myeloid Leukemia (AML).

What treatments are being tested in NCT05662904?

The interventions being studied include: Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion (BIOLOGICAL), Gemtuzumab Ozogamicin (DRUG). CD33-deleted CD34+ hematopoietic stem cells derived from the initially matched family donor

What does Phase 1 mean for NCT05662904?

Phase 1 trials are the first stage of testing a new treatment in humans. They focus on safety, dosage, and side effects, usually involving 20-100 healthy volunteers or patients.

What is the current status of NCT05662904?

This trial is currently "Not Yet Recruiting." It started on 2028-01. The estimated completion date is 2030-01.

Who is sponsoring NCT05662904?

NCT05662904 is sponsored by German Cancer Research Center. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT05662904?

The trial aims to enroll 12 participants. The trial has not yet started recruiting.

How is NCT05662904 designed?

This is a interventional study, uses na allocation, follows a single_group design, employs none masking.

What are the primary outcomes being measured in NCT05662904?

The primary outcome measures are: engraftement of gene edited CD34+HSC (on day 28); dose-limiting toxicity (until EOS (day 90)); toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) (until EOS (day 90)). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT05662904 being conducted?

This trial is being conducted at 2 sites, including Dresden; Heidelberg (Germany).

Where can I find official information about NCT05662904?

The official record for NCT05662904 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT05662904. This government database provides the most up-to-date and detailed information about the trial.

What is NCT05662904 testing in simple terms?

Tests a new method to remove CD33 from stem cells to improve CD33-directed immunotherapy for AML. For patients who have relapsed AML after a stem cell transplant from a family donor.

Why is this trial significant?

This trial aims to fill a gap in treatment options for relapsed AML by improving the effectiveness of existing immunotherapies.

What are the potential risks of participating in NCT05662904?

Potential risks include side effects from the treatment and the possibility of the treatment not working. Monitor for signs of infection and report any unusual symptoms to your healthcare provider. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT05662904?

Ask your doctor if you have relapsed AML and have had a stem cell transplant from a family donor. Participation involves receiving edited stem cells and regular check-ups to monitor your health. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT05662904 signal from an investment perspective?

The market for AML treatments is large, with limited options for relapsed patients, making this trial potentially significant. This is a Phase 1 trial, which is in early development stages.

What happens if the treatment in this trial doesn't work?

Participation involves receiving edited stem cells and monitoring for side effects and response to treatment. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

Related Conditions

More Relapsed/Refractory Acute Myeloid Leukemia (AML) Trials

View all Relapsed/Refractory Acute Myeloid Leukemia (AML) clinical trials

This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.