Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant
a study on Leukemia Acute Myeloid Leukemia Allogeneic Hematopoietic Cell Transplantation Hematopoietic Cell Transplantation
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at La Jolla, California and other locations
- Dates
- study startedcompletion around
- Principal Investigator
- by Divya Koura, MD
Description
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).
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
Details
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.
Keywords
Leukemia, Myeloid, Acute, 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, Myeloid Leukemia, VCAR33
Eligibility
You can join if…
Open to people ages 18 years and up
- 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 CAN'T join 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
Locations
- University of California San Diego Moores Cancer Center
accepting new patients
La Jolla California 92093 United States - Stanford Cancer Institute
accepting new patients
Stanford California 94305 United States
Lead Scientist at UCSD
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Vor Biopharma
- ID
- NCT05984199
- Phase
- Phase 1/2 research study
- Study Type
- Interventional
- Participants
- Expecting 24 study participants
- Last Updated
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