AzTrials
AzTrials

Leukemia, Myeloid, AcutePhase 1/2NCT05984199

Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant

A Phase 1/2 study testing VCAR33 in people with Leukemia, Myeloid, Acute, run by Vor Biopharma at 14 sites in United States.

Terminated

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

Official record
Search all trials

Trial summary

This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (alloHCT). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
VCAR33
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
14 sitesUnited States
Study dates
11 Dec 2023to 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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged ≥18 years
  • Patients must have CD33+ AML in relapse or refractory after alloHCT
  • Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101 study who have R/R AML may also be considered.
  • Disease status at the time of enrollment:
  • Arm A/Morphologic disease: Defined as ≥ 5% blasts (bone marrow) post-HCT
  • Arm B/MRD positive: < 5% blasts (bone marrow) with minimal residual disease of at least 0.1% CD33+ leukemia cells by flow cytometry
Show all 13Show fewer
  • Performance status: ECOG 0 or 1
  • Patient must have adequate organ function as defined by:
  • Cardiac: Left ventricular ejection fraction (LVEF) ≥ 45% or fractional shortening ≥ 28%
  • Pulmonary: Baseline oxygen saturation > 92% on room air at rest
  • Hepatic: Total bilirubin < 3x institutional upper limit of normal (ULN) (except in case of patients with documented Gilbert's disease < 5x ULN) and aspartate aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) < 5x institutional ULN
  • Renal: Serum creatinine must be ≤ 1.2x institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above institutional normal
  • Original alloHCT donor is available and willing to undergo apheresis

Who cannot join

  • Patients who have undergone more than one alloHCT
  • Patients who have undergone alloHCT with a mismatched unrelated donor, haploidentical donor, or with umbilical cord blood as the stem cell source
  • Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion.
  • Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD unless approved by the Sponsor Medical Monitor
  • Patients with evidence of ongoing active acute or chronic GVHD and are taking systemic immunosuppressive agents (> 10 mg daily of prednisone equivalent or other GVHD-directed treatment, including extracorporeal photopheresis). Patients with Grade 1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes, mouth, or skin controlled with only topical therapy are eligible.
  • Patients with active CNS disease. A lumbar puncture is not required to exclude CNS disease in the absence of clinical signs or symptoms suggesting CNS disease.
Show all 13Show fewer
  • Patients with the following prior therapy:
  • DLI within 28 days prior to enrollment
  • Prior treatment with any CAR T cell therapy product
  • Patients with active or uncontrolled viral, bacterial, or fungal infection
  • Patients with a history of a human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection
  • Patients with a history of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, or breast) unless disease free for at least 3 years after the last definitive therapy
  • Female patients of childbearing potential who are pregnant or breastfeeding

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • University of Michigan Health

    Ann Arbor, Michigan, 48109

  • 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

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • 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, 92093

  • Miami Cancer Institute

    Miami, Florida, 33176

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • University of Utah Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Washington University School of Medicine Siteman Cancer Center

    St Louis, Missouri, 63110

  • Stanford Cancer Institute

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients With Relapsed or Refractory Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation

This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (alloHCT).

Read the detailed description

CD33 is a preferential target for AML CAR T cell therapy due to its surface expression on the majority (>80%) of AML blasts and due to the extensive prior clinical experience demonstrating safety and efficacy of targeting CD33 with Mylotarg (gemtuzumab ozogamicin). VCAR33 is being developed as a potential new treatment for patients with relapsed/refractory (R/R) AML after alloHCT. In this Phase 1/2 trial, the safety and efficacy of lentiviral-transduced CD33-directed CAR T cells (VCAR33) generated from the patient's prior allogeneic stem cell donor will be tested. It is hypothesized that CAR T cell production from healthy donors will not only eliminate delays in production due to lymphopenia but also reduce concerns for suboptimal T cell function from exposure to systemic immunosuppression or chemotherapeutic agents. Approximately 24 eligible patients with R/R AML after alloHCT will be enrolled in one of two separate arms based on disease burden (morphologic disease versus measurable residual disease (MRD ) positive). The maximum tolerated dose of VCAR33 will be determined using a 3+3 trial design within each arm. Dose escalation can only occur after a minimum of 3 patients have completed the dose-limiting toxicity (DLT) observation period.

Being tested
VCAR33
Keywords
Leukemia, Acute Myeloid Leukemia, AML, Hematopoietic stem cell transplant, HCT, CD33, Allogeneic, CAR T, CAR-T, Chimeric Antigen Receptor T Cell, CAR T Cells, CAR-T Cells, Immunotherapy
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia

What participants receive

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

  • VCAR33Biological

    Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy

Study groups in NCT05984199
Study groupRoleWhat they receive
Morphologic Disease: Cohort 1ExperimentalVCAR33 Dose Level 1
Receives: Biological: VCAR33
Morphologic Disease: Cohort 2ExperimentalVCAR33 Dose Level 2
Receives: Biological: VCAR33
Morphologic Disease: Cohort 3ExperimentalVCAR33 Dose Level 3
Receives: Biological: VCAR33
MRD Positive: Cohort 1ExperimentalVCAR33 Dose Level 1
Receives: Biological: VCAR33
MRD Positive: Cohort 2ExperimentalVCAR33 Dose Level 2
Receives: Biological: VCAR33
MRD Positive: Cohort 3ExperimentalVCAR33 Dose Level 3
Receives: Biological: VCAR33

What is being measured

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

  1. Incidence of dose-limiting toxicities

    Measured: Day 28

Secondary outcomes (4)

  1. Incidence of GVHD related to VCAR33

    Measured: Up to 24 months

  2. Percentage of patients who achieve response

    Measured: Up to 24 months

  3. Overall survival post-VCAR33 infusion

    Measured: Up to 24 months

  4. Progression-free survival post-VCAR33 infusion

    Measured: Up to 24 months

Timeline

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

  1. First posted9 Aug 2023
  2. Study start11 Dec 2023
  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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05984199
Sponsor's protocol ID
VBP301
Status last verified
May 2025
First submitted
19 Jul 2023
Last updated
29 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mushtaq MU, DiPersio JF, Azzi J, Cooper BW, Koehne G, Koura D, Maakaron J, Magenau J, McClune B, Rimando JC, Shah NN, Suh HC, Beuka K, Sturrock J, Nikam M, Berglund E, Hu J, Keschner Y, Etchin J, Lydeard JR, Vasquez M, O'Donnell D, Mundelboim G, Thosar S, Canesin G, Xavier-Ferrucio J, Hyzy SL, Lloyd DM, Spink K, Hummel D, Lee-Sundlov MM, Scherer J, Lin MI, Whangbo JS, Muffly LS. A phase 1/2 study of donor-derived anti-CD33 CAR T-cell therapy (VCAR33) for relapsed/refractory AML after allogeneic HCT. Blood. 2026 Apr 23;147(17):1914-1927. doi: 10.1182/blood.2025031053.

    PubMed 41636724

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VCAR33 in people with Leukemia, Myeloid, Acute, run by Vor Biopharma at 14 sites in United States.

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 13 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 14 sites in United States. 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 dose-limiting toxicities (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 NCT05984199, which also lists 1 linked publication.

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.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in