cd33-car t cell therapy for the treatment of recurrent or refractory acute myeloid leukemia

Conditions: Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Summary: 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.

Eligibility criteria:
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 allowed if \> 6 months prior to study enrollment * participant must have a confirmed diagnosis of active cd33+ aml de novo, 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) 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 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 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 negative * donor: kps \>= 70 * donor: documented body weight exclusion criteria: * 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 * with exception to hydrea which must be stopped prior to initiation of lymphodepletion * research participants on active systemic antifungal treatment within 8 weeks of enrollment are not eligible. however, participants on antifungal prophylaxis are eligible * not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis * 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)