NCT05984199

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

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 38 (actual)
• Sponsor: Vor Biopharma · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

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.

Conditions

• Leukemia, Myeloid, Acute

Interventions

Type	Name	Description
BIOLOGICAL	VCAR33	Allogeneic Anti-CD33 Chimeric Antigen Receptor (CAR) T Cell therapy

Timeline

• Start date: 2023-12-11
• Primary completion: 2025-05-28
• Completion: 2025-05-28
• First posted: 2023-08-09
• Last updated: 2025-07-29

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study