CD33-CAR T Cell Therapy for the Treatment of Recurrent or Refractory Acute Myeloid Leukemia

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.

Inclusion Criteria:Documented informed consent of the participant and/or legally authorized representativeAssent, when appropriate, will be obtained per institutional guidelinesFor 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 processedAgreement to allow the use of archival tissue from diagnostic tumor biopsiesIf unavailable, exceptions may be granted with Study principal investigator (PI) approvalAge: >= 18 yearsKarnofsky Performance Scale (KPS) >= 70Life expectancy >= 16 weeks at the time of enrollmentPrior allogeneic transplant allowed if > 6 months prior to study enrollmentParticipant must have a confirmed diagnosis of active CD33+ AML de novo, or secondary OR participants who are at a high risk for disease recurrenceRelapsed AML is defined as patients that had a first complete response (CR) before developing recurrent disease (increased bone marrow blasts)Refractory AML is defined as patients that have not achieved a first CR after induction chemotherapy. For patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapyResearch participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AMLCD33 positivity must be confirmed by either flow cytometry or immunohistochemistry within 90 days of study entry. Cytogenetics, flow cytometry, and molecular studies (such as FLT-3 status) will be obtained as per standard practiceResearch participants who are at a high risk of disease recurrence, they must have historical bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AMLNo known contraindications to lymphodepleting agents, steroids, tocilizumab and/or cetuximab, or the investigational agentTotal serum bilirubin =< 2.0 mg/dLParticipants with Gilbert syndrome may be included if their total bilirubin is =< 3.0Aspartate aminotransferase (AST) =< 3 x the upper limit of normal (ULN)Alanine aminotransferase (ALT) =< 3 x ULNEstimated creatinine clearance of >= 60 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysisLeft ventricular ejection fraction >= 50% within 8 weeks before enrollmentOxygen (O2) saturation > 92% not requiring oxygen supplementationWomen of childbearing potential (WOCBP): negative urine or serum pregnancy testIf the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be requiredAgreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapyChildbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)Research participants must have a potential donor or stem cell source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical)DONOR: The identified donor must be the original donor whose stem cells were used for the research participant's allogeneic hematopoietic stem cell transplantation (alloSCT)DONOR: The donor must be HIV negativeDONOR: KPS >= 70DONOR: Documented body weightExclusion Criteria:Prior allogeneic transplant if < 6 months prior to enrollmentConcurrent 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 allowedParticipants with active autoimmune disease, including graft versus host disease (GvHD), requiring systemic immune suppressive should be stopped 28-days prior to enrollmentParticipants may not be receiving any other investigational agents and are not dependent on concurrent biological therapy, chemotherapy, or radiation therapyWith exception to Hydrea which must be stopped prior to initiation of lymphodepletionResearch participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. However, participants on antifungal prophylaxis are eligibleNot applicable at the time of enrollment if the research participant's donor is undergoing leukapheresisSubjects with >= Grade 2 myelofibrosis on bone marrow biopsySubjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening if the patient is undergoing leukapheresis. Patients with controlled atrial arrythmia is allowedKnown bleeding disorders (e.g., von Willebrand's disease) or hemophiliaHistory of stroke or intracranial hemorrhage within 6 months prior to screeningSubjects with presence of other active malignancy, however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligibleClinically significant uncontrolled illnessActive infection requiring antibioticsResearch participants who have tested human immunodeficiency virus (HIV) positive, or have active hepatitis B or C infection based on testing performed within 4 weeks of enrollmentActive viral hepatitisFemales only: Pregnant or breastfeedingAny other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study proceduresProspective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)