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

NCT05984199 | Terminated Phase 1 FDA Drug

• 1 other identifier: VBP301
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 14

Brief 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).

Conditions

Leukemia, Myeloid, Acute

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

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Day 28

Secondary Outcomes (4)

• Incidence of GVHD related to VCAR33

  Up to 24 months

• Percentage of patients who achieve response

  Up to 24 months

• Overall survival post-VCAR33 infusion

  Up to 24 months

• Progression-free survival post-VCAR33 infusion

  Up to 24 months

Study Arms (6)

Morphologic Disease: Cohort 1

EXPERIMENTAL

VCAR33 Dose Level 1

Biological: VCAR33

Morphologic Disease: Cohort 2

EXPERIMENTAL

VCAR33 Dose Level 2

Biological: VCAR33

Morphologic Disease: Cohort 3

EXPERIMENTAL

VCAR33 Dose Level 3

Biological: VCAR33

MRD Positive: Cohort 1

EXPERIMENTAL

VCAR33 Dose Level 1

Biological: VCAR33

MRD Positive: Cohort 2

EXPERIMENTAL

VCAR33 Dose Level 2

Biological: VCAR33

MRD Positive: Cohort 3

EXPERIMENTAL

VCAR33 Dose Level 3

Biological: VCAR33

Interventions

VCAR33 BIOLOGICAL

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

MRD Positive: Cohort 1; MRD Positive: Cohort 2; MRD Positive: Cohort 3; Morphologic Disease: Cohort 1; Morphologic Disease: Cohort 2; Morphologic Disease: Cohort 3

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Vor Biopharma: lead

Study Sites (14)

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

National Institutes of Health, Clinical Center

Bethesda, Maryland, 20892, United States

Location

University of Michigan Health

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Mushtaq MU, DiPersio JF, Azzi J, Cooper BW, Koehne G, Koura D, Maakaron JE, Magenau JM, McClune B, Rimando JC, Shah NN, Suh HC, Beuka K, Sturrock J, Nikam MH, Berglund E, Hu J, Keschner Y, Etchin J, Lydeard JR, Vasquez MD, 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 Feb 4:blood.2025031053. doi: 10.1182/blood.2025031053. Online ahead of print.

  PMID: 41636724 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2023
• First Posted: August 9, 2023
• Study Start: December 11, 2023
• Primary Completion: May 28, 2025
• Study Completion: May 28, 2025
• Last Updated: July 29, 2025

Record last verified: 2025-05

Locations

US (14)