CD83 CAR T in Relapsed or Refractory Acute Myeloid Leukemia (AML): A Phase I Trial
This phase I trial tests the safety, side effects, and best dose of genetically engineered cells (CD83 chimeric antigen receptor \[CAR\] T cells) in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). CD83 is a protein that is found on AML blasts. Blasts are abnormal immature white blood cells that can multiply uncontrollably: filling up the bone marrow and preventing the production of other cells important for survival. CD83 CAR T cells represent a new cell therapy to eliminate AML blasts, while avoiding the risk for graft versus host disease (GVHD) after stem cell transplant to replace bone marrow or, tumor toxicity like myeloid aplasia where the body's own immune system causes damage to the bone marrow stem cells. Therefore, human CD83 CAR T cells are a promising cell-based approach to preventing two critical complications of stem-cell transplant - GVHD and relapse. Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML.
• Age ≥ 18 years old.
• Karnofsky performance status score ≥ 70%.
• Relapsed or refractory AML based upon ELN 2022 criteria.
• Creatinine clearance: ≥ 40 mL/min (Cockroft-Gault).
• Total bilirubin: ≤ 2mg/dL except for patients with Gilbert's syndrome, hemolysis, or related to disease.
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 3.0 x upper limit of normal (ULN).
• Left ventricular (LV) ejection fraction: \> 45% and be free of symptomatic congestive heart failure or uncontrolled arrhythmia.
• Oxygen (O2) saturation: ≥ 92% on room air without needs for supplemental O2.
• Absolute lymphocyte count: ≥ 0.2 x 10\^9/L, HCT of ≥ 27% and platelets of ≥ 20 x 10\^9/L. Transfusion support is allowed to meet HCT and platelet parameters prior to apheresis.
• Life expectancy ≥12 weeks from the time of enrollment, per clinical judgment.
• Negative serum pregnancy test in females of child-bearing potential (FOCBP). FOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.
• If history of allogeneic HCT, must have completed transplant at least 3 months prior, be off immunosuppression, including ruxolitinib, at least 2 weeks prior to apheresis, and have no evidence of GVHD requiring treatment at enrollment.
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 12 months following duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Participants must be considered preliminarily eligible for an allogeneic hematopoietic cell transplantation, with potential donors identified per a transplant and cellular therapy consult at Roswell Park Comprehensive Cancer Center.
• Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.