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

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