Acute Myeloid Leukemia Clinical Trial

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

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).

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Full 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.

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Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

24

Study ID:

NCT05984199

Recruitment Status:

Recruiting

Sponsor:

Vor Biopharma

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There are 10 Locations for this study

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University of California San Diego Moores Cancer Center
La Jolla California, 92093, United States More Info
Michelle Padilla
Contact
858-822-5364
[email protected]
Divya Koura, MD
Principal Investigator
Stanford Cancer Institute
Stanford California, 94305, United States More Info
Lori Muffly, MD
Contact
650-723-0822
[email protected]
Lori Muffly, MD
Principal Investigator
Miami Cancer Institute
Miami Florida, 33176, United States More Info
Guenther Koehne, MD, PhD
Contact
786-527-8427
[email protected]
Guenther Koehne, MD, PhD
Principal Investigator
The University of Kansas Cancer Center
Fairway Kansas, 66205, United States More Info
Muhammad U Mushtaq, MD
Contact
913-945-6594
[email protected]
Muhammad U Mushtaq, MD
Principal Investigator
University of Michigan Health
Ann Arbor Michigan, 48109, United States More Info
Gregory Yanik, MD
Contact
734-647-8902
[email protected]
Gregory Yanik, MD
Principal Investigator
Karmanos Cancer Institute
Detroit Michigan, 48201, United States More Info
Marie Ventimiglia
Contact
313-576-9271
[email protected]
Abhinav Deol, MD
Principal Investigator
Washington University School of Medicine Siteman Cancer Center
Saint Louis Missouri, 63110, United States More Info
Caroline Cartledge
Contact
314-273-8198
[email protected]
John DiPersio, MD
Principal Investigator
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack New Jersey, 07601, United States More Info
Andrew McConnell
Contact
551-996-5949
[email protected]
Hyung Suh, MD
Principal Investigator
University Hospitals Seidman Cancer Center
Cleveland Ohio, 44106, United States More Info
Cancer Information Service Line
Contact
800-641-2422
[email protected]
Brenda Cooper, MD
Principal Investigator
University of Utah Huntsman Cancer Institute
Salt Lake City Utah, 84112, United States More Info
Catherine Cromar
Contact
801-585-2626
[email protected]
Brian McClune, MD
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Phase:

Phase 1

Estimated Enrollment:

24

Study ID:

NCT05984199

Recruitment Status:

Recruiting

Sponsor:


Vor Biopharma

How clear is this clinincal trial information?

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