This phase I trial tests the safety, side effects, and the best dose of anti-CD33 chimeric antigen receptor (CAR) T-Cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient or donor's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's or donor's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers.
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening, while the request for a translated full consent is processed
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
Prior allogeneic transplant if < 6 months prior to enrollment
Concurrent use of systemic steroids or chronic use of immunosuppressant medications should be stopped 28-days prior to enrollment. Recent or current use of inhaled or topical steroids in standard doses is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg/day, or equivalent doses of other corticosteroids) is allowed
Participants with active autoimmune disease, including graft versus host disease (GvHD), requiring systemic immune suppressive should be stopped 28-days prior to enrollment
Participants may not be receiving any other investigational agents and are not dependent on concurrent biological therapy, chemotherapy, or radiation therapy
Single group
Anti-CD33 CAR T-cells
Biological/VaccineGiven IV
Lymphodepletion Therapy
Procedure/SurgeryUndergo lymphodepletion
Participants who achieve measurable residual disease (MRD)
Defined as complete response (CR) or MRD- complete response with incomplete hematopoietic recovery. Rates and associated 90% Clopper and Pearson binomial confidence limits.
Incidence of dose-limiting toxicities and full toxicity profile
Rates and associated 90% toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events version 5.0, and modified Cytokine Release Syndrome grading as applicable. Clopper and Pearson binomial confidence limits.
Expansion and persistence of the CAR T cell product
Descriptive statistics and graphical methods will be used to present expansion and persistence.
Percent and counts from peripheral blood cell subsets in hematopoietic stem/progenitor cell compartments
Descriptive statistics and graphical methods will be used to present T cell numbers and percentages over time.
Duration of response
Patients who have not had disease relapse/progression or death at the last follow-up will be censored at the time of last follow-up. Patients who never achieved CR will be excluded from the analysis. Descriptive statistics will be provided for duration of response.
Progression-free survival
Participants are considered a failure for this endpoint if they die (regardless of cause) or experience disease relapse.
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
