Genetically Engineered Cells (CD83 CAR T Cells) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
NCT ID: NCT06871410
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
26 participants
INTERVENTIONAL
2026-01-15
2028-04-01
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
Autologous Anti-CD83 CAR T-cells
Given IV
Biospecimen Collection
Undergo bone marrow aspiration blood sample collection
Chest Radiography
Undergo chest x-ray
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Echocardiography
Undergo ECHO
Fludarabine Phosphate
Given IV
Hydroxyurea
Given hydroxyurea
Leukapheresis
Undergo leukapheresis
Lumbar Puncture
Undergo lumbar puncture
Positron Emission Tomography
Undergo PET
Questionnaire Administration
Ancillary studies
Interventions
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Autologous Anti-CD83 CAR T-cells
Given IV
Biospecimen Collection
Undergo bone marrow aspiration blood sample collection
Chest Radiography
Undergo chest x-ray
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Echocardiography
Undergo ECHO
Fludarabine Phosphate
Given IV
Hydroxyurea
Given hydroxyurea
Leukapheresis
Undergo leukapheresis
Lumbar Puncture
Undergo lumbar puncture
Positron Emission Tomography
Undergo PET
Questionnaire Administration
Ancillary studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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 any treatments other than hydroxyurea, hypomethylating agents, 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.
18 Years
ALL
No
Sponsors
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Roswell Park Cancer Institute
OTHER
Responsible Party
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Principal Investigators
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Shernan G Holtan
Role: PRINCIPAL_INVESTIGATOR
Roswell Park Cancer Institute
Locations
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Roswell Park Cancer Institute
Buffalo, New York, United States
Countries
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Facility Contacts
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Shernan G. Holtan
Role: primary
Other Identifiers
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NCI-2025-01523
Identifier Type: REGISTRY
Identifier Source: secondary_id
I-3916824
Identifier Type: OTHER
Identifier Source: secondary_id
I-3916824
Identifier Type: -
Identifier Source: org_study_id