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

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Lumbar Puncture; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Leukapheresis; Procedure: Positron Emission Tomography; Procedure: Echocardiography; Drug: Fludarabine Phosphate; Procedure: Chest Radiography; Drug: Autologous Anti-CD83 CAR T-cells; Procedure: Biospecimen Collection; Drug: Hydroxyurea

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety and determine the maximal tolerated dose (MTD) of autologous anti-CD83 CAR T-cells (CD83 CAR T cells) administered as a single infusion to refractory/relapsed acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

I. To observe and record activity against AML. II. To evaluate response for AML using 2022 European Leukemia Net (ELN) criteria.

III. To evaluate progression-free and overall survival after CAR T cell infusion.

IV. To evaluate the time to hematological recovery after CAR T cell infusion. V. To evaluate in vivo CAR T cell expansion and persistence. VI. To evaluate acute GVHD within 6 weeks after infusion of CAR T cells in patients who relapsed after allogeneic hematopoietic cell transplantation (HCT).

VII. To evaluate the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

EXPLORATORY OBJECTIVES:

I. To evaluate the relationship between cytokine expression and cytokine release syndrome (CRS).

II. To determine predictors of response and mechanisms or resistance to CAR-T cells.

III. To evaluate immune effects by CD83 CAR T cells on peripheral blood T cell subsets, B cells and dendritic cells.

IV. To evaluate the relationship between baseline levels of CD83 expression on AML blasts and response following CAR T cell infusion.

V. To evaluate the relationship between proportion of infused CAR T cell subsets (γδ T cells versus [vs.] αβ T cells) and disease response.

VI. To evaluate immunity after CAR T cell infusion. VII. To determine the rate of successful manufacturing and time required to complete.

VIII. To evaluate for CAR T phenotype, exhaustion, and CAR versus non-CAR subsets associated with response and relapse.

IX. Evaluate the effect of CAR T infusion on quality of life.

OUTLINE:

Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for CD83 CAR T cell product manufacturing on day -21 and may receive hydroxyurea at the discretion of the treating physician on study. Patients then receive fludarabine intravenously (IV) over 30 minutes and cyclophosphamide IV over 2 hours on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive CD83 CAR T cells IV over 15 minutes on day 0. Patients also undergo echocardiography (ECHO) and chest x-ray during screening, blood sample collection throughout the study, and computed tomography (CT) and/or positron emission tomography (PET), as well as lumbar puncture as clinically indicated. In addition, patients may undergo bone marrow aspiration throughout the study.

After completion of study treatment, patients are followed up every 2 weeks for 2 months then at 3, 6, and 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: ASK RPCI; Phone Number: 800-767-9355; Email: askrpci@roswellpark.org
      • Principal Investigator: Shernan G. Holtan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (fludarabine, cyclophosphamide, CD83 CAR T-cells); Patients undergo leukapheresis to obtain PBMCs for CD83 CAR T-cell product manufacturing on day -21 and may receive hydroxyurea at the discretion of the treating physician on study. Patients then receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -5 to -3 in the absence of disease progression or unacceptable toxicity. Patients then receive CD83 CAR T-cells IV over 15 minutes on day 0. Patients also undergo ECHO and chest x-ray during screening, blood sample collection throughout the study, and CT and/or PET, as well as lumbar puncture as clinically indicated. In addition, patients may undergo bone marrow aspiration throughout the study.

Other: Questionnaire Administration; Ancillary studies; Procedure: Lumbar Puncture; Undergo lumbar puncture; Other Names: LP; Spinal Tap; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Asta B 518; B-518; WR-138719; B 518; B518; WR 138719; WR138719; Procedure: Leukapheresis; Undergo leukapheresis; Other Names: Leukocytopheresis; Therapeutic Leukopheresis; Leukocyte Adsorptive Apheresis; White Blood Cell Reduction Apheresis; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Echocardiography; Undergo ECHO; Other Names: EC; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP; Beneflur; Fludara; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; SH T 586; Procedure: Chest Radiography; Undergo chest x-ray; Other Names: Chest X-ray; Drug: Autologous Anti-CD83 CAR T-cells; Given IV; Other Names: Autologous Anti-CD83 CAR T Cells; Autologous Anti-CD83 CAR-T Cells; Procedure: Biospecimen Collection; Undergo bone marrow aspiration blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Hydroxyurea; Given hydroxyurea; Other Names: Hydrea; Hydroxycarbamide; Droxia; Litalir; Onco-Carbide; Oncocarbide; Oxeron; SQ 1089; SQ-1089; Syrea; WR 83799

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicity (DLT)	Will be defined as any adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Cytokine release syndrome(CRS)/immune effector cell-associated neurotoxicity syndrome will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Guidelines. The DLTs will be summarized by dose level using frequencies and relative frequencies. Will employ the Bayesian optimal interval design to find the maximal tolerated dose (MTD). The target DLT rate for the MTD is = 0.33.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response	Will be determine as the number of patients achieving complete remission, partial remission, and/or morphologic leukemia free state by 2022 European Leukemia Net Response Criteria. Will be summarized by dose level using frequencies and relative frequencies. Rates will be estimated using 95% credible regions obtained by Jeffrey's prior method. As exploratory analyses, comparisons between dose levels may be made using Fisher's exact test.	At 28 days and 1 year
Overall survival	Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.	From treatment initiation until death due to any cause or last follow-up, assessed up to 1 year
Progression-free survival	Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.	From treatment initiation until disease progression/relapse, death due to any cause, subsequent treatment (censored), or last follow-up, assessed up to 1 year
Hematologic recovery	Will be assessed by achieving an absolute neutrophil count recovery (> 0.5 x 10^9/L). Will be summarized by dose level using frequencies and relative frequencies. Rates will be estimated using 95% credible regions obtained by Jeffrey's prior method. As exploratory analyses, comparisons between dose levels may be made using Fisher's exact test.	At 28 days
Time to hematologic recovery	Relapse or death will be considered the competing risk. Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.	From treatment initiation until hematologic recovery or last follow-up, assessed up to 1 year
Acute graft-versus-host disease (GVHD)	Will be defined as a grade II-IV acute GVHD. Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.	Up to 6 weeks
Time to GVHD	Relapse or death will be considered the competing risk. Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.	From treatment initiation until grade II-IV GVHD, 6 weeks post infusion, or last follow-up, assessed up to 1 year
Treatment-related adverse events	Will be defined as by CTCAE v5 and CRS by ASTCT Consensus Grading for CRS and Neurological Toxicity Associated with Immune Effector Cells. Will be summarized by dose level using frequencies and relative frequencies. Rates will be estimated using 95% credible regions obtained by Jeffrey's prior method. As exploratory analyses, comparisons between dose levels may be made using Fisher's exact test.	Up to 12 months
Time to treatment related adverse event	Relapse or death will be considered the competing risk. Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate	From treatment initiation until a treatment related adverse event, 12 months post infusion, or last follow-up, assessed up to 1 year
Number of peripheral blood chimeric antigen receptor (CAR) T cells	Will be summarized by dose level and timepoint (pre- and post-therapy) using the mean, median, and standard deviation; and graphically using dot plots. The log absolute number of CD83 CAR T cells per peripheral blood volume will be modeled as a function of dose level, time, their two-way interaction, and a random subject effect using a linear mixed model. Tests about the appropriate contrasts on model estimates will be sued to compare: 1) changes relative to pre-therapy within each dose level, and 2) changes at a given timepoint between dose levels. All model assumptions will be verified graphically, and transformations applied as appropriate.	Up to 1 year

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Shernan G Holtan, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 12, 2025

Study Record Updates

• Last Update Posted (Actual): August 17, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Cytological Techniques; Biopsy; Hydrocarbons; Physical Phenomena; Amides; Chemistry Techniques, Analytical; Spectrum Analysis; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Electromagnetic Phenomena; Magnetic Phenomena; Biological Therapy; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Diagnostic Techniques, Neurological; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Urea; Cyclophosphamide; Hydroxyurea; Specimen Handling; Magnetic Resonance Spectroscopy; fludarabine phosphate; Leukapheresis; Spinal Puncture; X-Rays
• Other Study ID Numbers: I-3916824 (Roswell Park Cancer Institute); NCI-2025-01523 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDMRP-CA250315 (Other Grant/Funding Number: DoD)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes