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Leukemia, Myeloid, AcutePhase 1/2NCT04849910

Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ AML or MDS

A Phase 1/2 study testing VOR33 and Mylotarg in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Vor Biopharma at 15 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase 1/2a, multicenter, open-label, first-in-human (FIH) study of VOR33 in participants with AML or MDS who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
VOR33 and Mylotarg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
15 sitesin 2 countries
Study dates
16 Dec 2021to 28 May 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must be ≥18 and ≤70 years of age.
  • Patients with AML must have one of the following groups of features that are known to be a risk factor for leukemia relapse:
  • BM in morphological remission (<5% blasts) with adverse-risk disease related genetics at presentation (according to European Leukemia-Net guidelines [ELN, Döhner 2017]), or
  • Intermediate risk genetics in morphologic remission (<5% blasts) with other recognized high risk criteria such as MRD+ following therapy, or
  • BM with evidence of persistent leukemia 5-10% blasts post induction/salvage therapy. Patients with BM Blast count >10% may participate with Sponsor Medical Monitor approval. (Note: these patients may have disease-related genetics of any risk criteria at presentation), or
  • Any patient in second or greater remission.
Show all 18Show fewer
  • Patients with MDS must have all of the following:
  • Previous or current IPSS-R score of High or Very High risk; AND
  • Previous or current MDS-IB1 or MDS-IB2 per the 2022 WHO criteria (Khoury 2022)
  • AML sample from the patient must have evidence of CD33 expression (>0%)
  • Candidate for HLA-matched allogeneic HCT using a myeloablative conditioning regimen.
  • Must have a related or unrelated stem cell donor that is a 8/8 match for HLA-A, -B, -C, and -DRB1.
  • Must have adequate performance status and organ function as defined below:
  • Performance Status: Karnofsky score of ≥70.
  • Cardiac: left ventricular ejection fraction (LVEF) ≥50%
  • Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) ≥66%.
  • Renal: estimated glomerular filtration rate (GFR) >60 mL/min
  • Hepatic: total bilirubin <1.5 × ULN, or if ≥1.5 × ULN direct bilirubin <ULN and ALT/AST <1.5 × ULN (per institutional criteria).

Who cannot join

  • Prior autologous or allogeneic stem cell transplantation.
  • Presence of the following disease-related genetics: t(15; 17)(q22; q21), or t(9; 22)(q34; q11), or other evidence of acute promyelocytic leukemia or chronic myeloid leukemia.
  • Prior treatment with Mylotarg™ (gemtuzumab ozogamicin) in the past 3.5 months.
  • Active central nervous system (CNS) leukemia.
  • Patients diagnosed with Gilbert's syndrome.
  • Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Winship Cancer Institute Emory University

    Atlanta, Georgia, 30322

  • National Institutes of Health, Clinical Center

    Bethesda, Maryland, 20892

  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

  • The University of Kansas Cancer Center

    Fairway, Kansas, 66205

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of California San Diego Moores Cancer Center

    La Jolla, California, 92037

  • Miami Cancer Institute

    Miami, Florida, 33176

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Utah Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • Washington University School of Medicine Siteman Cancer Center

    St Louis, Missouri, 63110

  • Stanford Cancer Institute

    Stanford, California, 94305

Other trials in United States

Canada1 site

  • Hôpital Maisonneuve-Rosemont

    Montreal, Quebec, H1T2M4

Other trials in Canada

About this study

Official title: A First-In-Human, Open-Label, Multicenter Study of VOR33 in Patients With Acute Myeloid Leukemia Who Are at High-Risk for Leukemia Relapse Following Hematopoietic Cell Transplantation

This is a Phase 1/2a, multicenter, open-label, first-in-human (FIH) study of VOR33 in participants with AML or MDS who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT).

Read the detailed description

High risk acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) frequently relapses despite hematopoietic stem cell transplant (HCT). Post-HCT targeted therapy to reduce relapse is limited by toxicity to the engrafted cells. VOR33, an allogeneic CRISPR/Cas9 genome-edited hematopoietic stem and progenitor cell (HSPC) therapy product, lacking the CD33 protein, is being investigated for participants with CD33+ AML or MDS at high risk for relapse after HCT to allow post-HCT targeting of residual CD33+ acute AML cells using Mylotarg™ without toxicity to engrafted VOR33 cells. Participants will undergo a myeloablative HCT with matched related or unrelated donor CD34+-selected hematopoietic stem and progenitor cells (HSPCs) engineered to remove CD33 expression (VOR33 product). Mylotarg™ will be given after engraftment for up to 4 cycles. The primary endpoint assessing safety of VOR33 will be the incidence of successful engraftment at 28 days. Part 1 of this study will evaluate the safety of escalating Mylotarg™ dose levels to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 will expand the number of participants to evaluate the Mylotarg™ RP2D.

Being tested
VOR33, Mylotarg
Keywords
Leukemia, Acute Myeloid Leukemia, AML, Hematopoietic stem cell transplant, HCT, CD33, Allogeneic, Myelodysplastic Syndromes, Myelodysplastic Syndromes with excess blasts, MDS, MDS-EB, Cell therapy
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia

What participants receive

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

  • VOR33Biological

    Allogeneic, human leukocyte antigen (HLA) matched, genome edited hematopoietic stem and progenitor cell (HSPC) therapy product lacking the CD33 myeloid protein

  • MylotargDrug

    Also called gemtuzumab ozogamicin

    Infusion of Mylotarg

Study groups in NCT04849910
Study groupRoleWhat they receive
Cohort 1ExperimentalVOR33 infusion followed by Mylotarg Dose Level 1
Receives: Biological: VOR33; Drug: Mylotarg
Cohort 2ExperimentalVOR33 infusion followed by Mylotarg Dose Level 2
Receives: Biological: VOR33; Drug: Mylotarg
Cohort 3ExperimentalVOR33 infusion followed by Mylotarg Dose Level 3
Receives: Biological: VOR33; Drug: Mylotarg

What is being measured

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

  1. Incidence of neutrophil engraftment

    Cumulative incidence of patients who achieve neutrophil engraftment (first day of 3 consecutive days of absolute neutrophil count (ANC) ≥500 cells/mm3) by Day 28.

    Measured: Day 28

Secondary outcomes (10)

  1. Time to neutrophil engraftment

    Time to neutrophil engraftment after HCT from Day 0; calculated as the first day of 3 consecutive laboratory values obtained on separate days where the ANC is ≥500 cells/mm3.

    Measured: Up to approximately 28 days

  2. Time to platelet recovery

    Time to platelet recovery defined as first day of a sustained platelet count >20,000/ μL with no platelet transfusion in the preceding seven days.

    Measured: Up to approximately 60 days

  3. Incidence of acute GVHD Grade (G) G2-G4 and G3-G4

    Measured: Up to 24 months

  4. Incidence of chronic GVHD (all and moderate-severe)

    Measured: Up to 24 months

  5. Incidence of primary and secondary graft failure

    Incidence of primary and secondary graft failure measured by day 28 post HCT. Secondary graft failure is defined as initial neutrophil engraftment by Day 28 followed by subsequent decline.

    Measured: Up to 24 months

  6. Incidence of toxicities to determine the MTD and RP2D of Mylotarg™

    Measured: Approximately day 60 until 24 months

  7. Incidence of transplant-related mortality (TRM) post HCT

    Measured: Day 100, 12 months, 24 months

  8. Percentage of CD33-negative myeloid cells

    Percent donor myeloid chimerism and CD33-negative myeloid cells in peripheral blood.

    Measured: Day 28, 60, 100, 180, and Months 12 and 24

  9. Relapse-free Survival (RFS)

    Cumulative incidence of RFS

    Measured: Months 12 and 24

  10. Overall Survival (OS)

    OS defined as the time from HCT to the date of death from any cause

    Measured: Months 12 and 24

Timeline

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

  1. First posted19 Apr 2021
  2. Study start16 Dec 2021
  3. Primary completion28 May 2025
  4. Study completion28 May 2025

Why it stopped: Lack of Funding

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04849910
Sponsor's protocol ID
VBP101
Status last verified
May 2025
First submitted
25 Mar 2021
Last updated
29 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • DiPersio JF, Koehne G, Shah NN, Bernard L, Suh HC, Koura D, Tamari R, Mushtaq MU, Maakaron J, Rimando J, Kennedy VE, Patel SS, Hudson C, Loken MR, Slapak CA, Lloyd DM, Stanizzi DA, Lee-Sundlov MM, Thosar S, Mundelboim G, Guo G, Ge HG, Li BE, Xavier-Ferrucio J, Hyzy SL, Lin MI, Raffel GD, Cooper BW. CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a phase 1/2 trial. Nat Med. 2026 May;32(5):1763-1772. doi: 10.1038/s41591-026-04362-1. Epub 2026 May 12.

    PubMed 42120728

  • Lydeard JR, Lin MI, Ge HG, Halfond A, Wang S, Jones MB, Etchin J, Angelini G, Xavier-Ferrucio J, Lisle J, Salvadore K, Keschner Y, Mager H, Scherer J, Hu J, Mukherjee S, Chakraborty T. Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity. Mol Ther Methods Clin Dev. 2023 Oct 13;31:101135. doi: 10.1016/j.omtm.2023.101135. eCollection 2023 Dec 14.

    PubMed 38027064

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VOR33 and Mylotarg in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Vor Biopharma at 15 sites in 2 countries.

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 18 inclusion and 6 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: stopped early, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: Lack of Funding). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of neutrophil engraftment (time frame: Day 28). 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 NCT04849910, which also lists 2 linked publications.

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 29 Jul 2025.

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