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

Inclusion Criteria

• 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 * If unavailable, exceptions may be granted with Study principal investigator (PI) approval
• Age: >= 18 years
• Karnofsky Performance Scale (KPS) >= 70
• Life expectancy >= 16 weeks at the time of enrollment
• Prior allogeneic transplant and at least >= 6 months out from alloHCT prior to study treatment NOTE: Exceptions may be made for enrollment (i.e., leukapheresis), per PI discretion, if: * Lack of remission is suggestive < 6 months after transplant AND * High-risk of CD33-positive disease relapse is observed AND * Participant(s) meet all other study criteria
• Participant must have a confirmed diagnosis of active CD33+ AML de novo, acute leukemia of ambiguous lineage with myeloid features or secondary OR participants who are at a high risk for disease recurrence * Relapsed AML is defined as patients that had a first complete response (CR)/CRi before developing recurrent disease (increased bone marrow blasts). ** For patients with late relapse of AML beyond the first 18 months, only patients with poor tolerance of initial induction therapy or unwillingness to proceed to current available standard of care treatment will be eligible. * Refractory AML is defined as patients that have not achieved a first CR/CRi (i.e., after at least 2 courses of induction chemotherapy). For patients with AML evolving from myelodysplastic syndrome, they should have completed at least one cycle of induction chemotherapy
• Research participants must have bone marrow and/or peripheral blood samples available for confirmation of diagnosis of AML * CD33 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 practice * Research 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 AML
• No known contraindications to lymphodepleting agents, steroids, tocilizumab and/or cetuximab, or the investigational agent
• Total serum bilirubin =< 2.0 mg/dL
• Participants with Gilbert syndrome may be included if their total bilirubin is =< 3.0
• Aspartate aminotransferase (AST) =< 3 x the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) =< 3 x ULN
• Estimated creatinine clearance of >= 60 mL/min per the Cockcroft-Gault formula, and the participant is not on hemodialysis
• Left ventricular ejection fraction >= 50% within 8 weeks before enrollment
• Oxygen (O2) saturation > 92% not requiring oxygen supplementation
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Agreement 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 therapy * Childbearing 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 related donor or stem cell source identified for allogeneic transplantation, (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 negative
• DONOR: KPS >= 70
• DONOR: Documented body weight
• DONOR: The donor is approved and has completed the donor evaluation per institutional guidelines (as indicated in DACT 122 – Administrative Protocol for Allogeneic Hematopoietic Progenitor Cell, Apheresis [HPC(A)] Collections). Additionally, donor will also be screened for the following infectious diseases: * Epstein-Barr virus (EBV) by polymerase chain reaction (PCR) * Human herpes virus 6, 7, and 8 (HHV6, HHV7, HHV8) * Parvovirus B19 ** Note: Infectious disease (ID) test results for EBV by PCR, HHV6, HHV7, HHV8 and Parvovirus B19 are not necessary to proceed with the apheresis procedure but do have to be resulted and negative before participant CAR T infusion

Exclusion Criteria

• Acute promyelocytic leukemia (APL) patients with available standard care treatment
• Isolated extramedullary disease at the time of enrollment
• Active central nervous system (CNS) disease at enrollment
• 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 be receiving other disease-targeted therapeutic agents but must meet washout criteria prior to lymphodepletion
• Research participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. However, participants on antifungal prophylaxis are eligible
• Subjects with >= Grade 2 myelofibrosis on bone marrow biopsy
• Subjects 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 allowed
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to screening
• Subjects with presence of other active malignancy, however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Research 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 enrollment
• Active viral hepatitis
• Females only: Pregnant or breastfeeding
• Any 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 procedures
• Prospective 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)