Genetically Engineered Cells (CD83 CAR T Cells) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Prior treatment

• Concomitant systemic glucocorticoid use at a dose equivalent to \> 10 mg daily prednisone at the time of apheresis and/or within 4 weeks of CD83 CAR T infusion for any reasons other than GVHD.
• Patients enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives prior to leukapheresis, whichever is shorter.
• Prior solid organ transplant.

Other illness

• Active central nervous system (CNS) leukemia; patients with history of CNS leukemia in complete response (CR) are eligible.
• Ongoing uncontrolled serious infection, pulmonary disease or psycho/social concerns.
• HIV seropositivity or active hepatitis B or C infection within (defined by positive polymerase chain reaction \[PCR\]) 4 weeks of enrollment.
• Other active malignancy within 2 years of study entry, except for basal cell cancer of skin, cervical cancer treated surgically with curative intent or localized prostate cancer managed with observational approach.
• Active autoimmune disease requiring immunosuppressive therapy.
• Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.

Lab values

• Patients requiring agents or any treatments other than hydroxyurea, single agent cytarbine,hypomethylating agents with or without ventoclax and/or targeted agents (i.e., FLT3, IDH2 or IDH1 inhibitors) to control blast counts within 14 days or 5 half-lives (whichever is shorter) prior to lymphodepletion.

Other

• Diagnosis of acute promyelocytic leukemia (APL; AML M3 by French-American-British \[FAB\] classification).
• Active grade II-IV acute GVHD in patients with relapsed AML after HCT requiring treatment.
• Pregnant or nursing female participants.
• Unwilling or unable to follow protocol requirements.

• Age ≥ 18 years old.
• Karnofsky performance status score ≥ 70%.
• Relapsed or refractory AML.This can include detection of AML by morphologic, flow cytometric, or molecular means.(20).
  • Relapsed AML is defined as the reappearance of malignant blasts in the bone marrow, reappearance of malignant blasts in the peripheral blood, or development of extramedullary disease after a documented complete remission.
  • Refractory AML is defined as failure to achieve complete remission after at least one cycle of induction chemotherapy.
  • At least 15% of AML blasts must be positive for CD83 expression by flow cytometry.
• 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
• 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.