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.
PRIMARY OBJECTIVE: I. Examine the anti-tumor activity and safety of administering patient-specific donor-derived (allogeneic) CD33-CAR T cells following lymphodepletion in research participants with CD33+ recurrent/refractory (r/r) acute myeloid leukemia (AML). SECONDARY OBJECTIVE: I. Assess activity in the form of CAR T cell expansion and persistence, to assess impact on hematopoiesis, 6-month progression free survival (PFS 6mo) rate, duration of response, and 1-year overall survival (OS) rate. EXPLORATORY OBJECTIVES: I. Change from baseline in numbers of CD33+ blood cells, CD33 expression on leukemia cells and hematopoietic cells. II. For subjects who receive cetuximab for CAR T cell ablation, assess the activity of infusional cetuximab to eliminate transferred CD33R(CD8h)BBzeta/EGFRt+ T cells. OUTLINE: This is a dose-escalation study. Patients undergo lymphodepletion therapy 3-5 days prior to CAR T cell infusion and receive anti-CD33 CAR T-cells intravenously (IV) on day 0. Patients with persistent CD33+ AML who are \> 28 days past the initial CAR T infusion, have additional product available and did not experience a dose-limiting toxicity, may optionally receive anti-CD33 CAR T-cells IV.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Given IV
Undergo lymphodepletion
City of Hope Medical Center
Duarte, California, United States
RECRUITINGParticipants 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.
Time frame: Up to 15 years post study treatment
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.
Time frame: Up to 1 year following the last CAR T cell infusion
Expansion and persistence of the CAR T cell product
Descriptive statistics and graphical methods will be used to present expansion and persistence.
Time frame: Up to 15 years post-CAR T cell infusion
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.
Time frame: Up to 15 years post-CAR T cell infusion
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.
Time frame: From the first achievement of CR after CAR T cell infusion through disease relapse or progression or death, assessed up to 15 years post CAR T cell infusion
Progression-free survival
Participants are considered a failure for this endpoint if they die (regardless of cause) or experience disease relapse.
Time frame: From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 15 years post CAR T cell infusion
Overall survival
Participants are considered a failure for this endpoint if they die, regardless of cause.
Time frame: from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years post CAR T cell infusion
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