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

Summary

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.

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.

Arms & interventions

• DrugAutologous Anti-CD83 CAR T-cells

  Given IV

• ProcedureBiospecimen Collection

  Undergo bone marrow aspiration blood sample collection

• ProcedureChest Radiography

  Undergo chest x-ray

• ProcedureComputed Tomography

  Undergo CT

• DrugCyclophosphamide

  Given IV

• ProcedureEchocardiography

  Undergo ECHO

• DrugFludarabine Phosphate

  Given IV

• DrugHydroxyurea

  Given hydroxyurea

• ProcedureLeukapheresis

  Undergo leukapheresis

• ProcedureLumbar Puncture

  Undergo lumbar puncture

• ProcedurePositron Emission Tomography

  Undergo PET

• OtherQuestionnaire Administration

  Ancillary studies

Outcome measures

Eligibility criteria