CD83-targeted CAR T cell therapy for adults with relapsed or refractory acute myeloid leukemia

CD83 CAR T in Relapsed or Refractory Acute Myeloid Leukemia (AML): A Phase I Trial

This Phase 1 trial tests a personalized CD83-targeted CAR T-cell infusion to try to eliminate leukemia cells in adults whose AML has relapsed or not responded to prior treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Roswell Park Cancer Institute (Academic / other)
• Drugs / interventions: ruxolitinib, CAR T, prednisone, chimeric antigen receptor, CAR-T, cyclophosphamide, fludarabine
• Locations: 1 site (Buffalo, New York)
• Trial ID: NCT06871410 on ClinicalTrials.gov

What this trial studies

This Phase 1, single-center trial gives patients autologous CD83-directed CAR T cells as a single infusion with a dose-escalation design to determine the maximum tolerated dose and safety. Participants undergo apheresis to collect T cells, receive lymphodepleting chemotherapy (including cyclophosphamide), and are closely monitored for toxicities such as cytokine release syndrome, neurotoxicity, and graft-versus-host disease in previously transplanted patients. Secondary endpoints include response by 2022 ELN criteria, progression-free and overall survival, time to hematologic recovery, and in vivo CAR T expansion and persistence. Exploratory studies will analyze cytokine patterns, baseline CD83 expression on blasts, and the composition of infused CAR T-cell subsets to identify predictors of response or resistance.

Who should consider this trial

Good fit: Adults (≥18 years) with relapsed or refractory AML by ELN 2022 criteria who have adequate organ function, Karnofsky performance status ≥70%, sufficient counts for apheresis, and a life expectancy of at least 12 weeks are ideal candidates.

Not a fit: Patients with severe organ dysfunction, poor performance status, inability to undergo apheresis or lymphodepletion, active infection or pregnancy, or leukemia lacking CD83 expression are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this therapy could offer a targeted way to eliminate AML blasts while lowering the risks of graft-versus-host disease and prolonged myeloid aplasia.

How similar studies have performed: CAR T-cell therapy has been highly successful in lymphoid cancers but AML-targeted CAR T approaches are early and have shown mixed results, and CD83 targeting is a relatively novel strategy with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Diagnosis of acute promyelocytic leukemia (APL; AML M3 by French-American-British \[FAB\] classification).
* Active central nervous system (CNS) leukemia; patients with history of CNS leukemia in complete response (CR) are eligible.
* Patients enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives prior to leukapheresis, whichever is shorter.
* 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.
* 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 grade II-IV acute GVHD in patients with relapsed AML after HCT requiring treatment.
* Prior solid organ transplant.
* Active autoimmune disease requiring immunosuppressive therapy.
* Pregnant or nursing female participants.
* Unwilling or unable to follow protocol requirements.
* Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.

Where this trial is running

Buffalo, New York

• Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)

Study contacts

• Principal investigator: Shernan G Holtan — Roswell Park Cancer Institute

Conditions Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia