FT538 in Combination with Daratumumab for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Acute myeloid leukemia relapsed/refractory after 2 lines of therapy; with CD38 expression * CD38 expression is defined by >= 20% of malignant cells with CD38 expression by flow cytometry on the most recent marrow biopsy (within 30 days of enrollment - archived or fresh) * Relapsed/refractory is defined as failure to achieve at least a Morphological Leukemia Free State (MLFS) or reverting from MLFS * Lines of therapy are defined as (must have had 2 prior therapies): ** One cycle of an Intensive induction chemotherapy such as 7+3, 5+2, mitoxantrone, etoposide, and cytarabine (MEC), fludarabine, high-dose cytarabine and filgrastim (FLAG), fludarabine, high-dose cytarabine, filgrastim, and idarubicin (FLAG-Ida), or cladribine, cytarabine and filgrastim (CLAG) +/- small molecule inhibitor ** Four weeks of HMA-based induction +/- small molecule inhibitor ** Hematopoietic stem cell transplantation (HSCT), must be > 90 days post ** Gemtuzumab ozogamicin ** Low-dose cytarabine (LDAC) + glasdegib ** Biomarker-specific targeted agents (FLT3 inhibitors, IDH1/2 inhibitors, others if available) ** Other treatments could be considered after discussion with the principal investigator (PI)
• Age 12 years or older at the time of consent - Please note, enrollment of minors will be begin until permission to proceed is received from the Food and Drug Administration (FDA) * At that time, the protocol will be updated to open enrollment to minors
• Weight >= 50 kg due to FT538 fixed cell dosing and FT538 product pre-dose packaging
• Karnofsky performance status of 80-100% for 16 years and older or Lansky Play Score of 80-100 for >= 12 and < 16 years of age
• Estimated glomerular filtration rate (estimated creatinine clearance) >= 50 mL/min/1.73m^2 (within 14 days of starting study treatment)
• Total bilirubin =< 5 x upper limit normal (ULN), not applicable for patients with Gilbert's syndrome (within 14 days of starting study treatment)
• Aspartate aminotransferase (AST) =< 3 x ULN and alanine aminotransferase (ALT) =< 3 x ULN, not applicable if determined to be directly due to underlying malignancy (within 14 days of starting study treatment)
• Left ventricular ejection fraction (LVEF) >= 40% by echocardiogram or multigated acquisition (MUGA) (within 14 days of starting study treatment)
• Contraceptive use by men or women * Female subjects: Women of childbearing potential (WOCBP) must use a highly effective form of contraception from the screening visit until at least 12 months after the final dose of cyclophosphamide (CY), at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest * Male subjects: Males with a female partner of childbearing potential or a pregnant female partner must be sterile (biologically or surgically) or use a highly effective method of contraception from the screening visit until at least 4 months after the final dose of CY and at least 4 months after the final dose of FT538, and at least 3 months after the final dose of daratumumab, whichever is latest
• Must agree to and sign the consent for the companion Long-Term Follow-Up study (UMN CPRC #2020LS220) to fulfill the FDA required 15 years of follow-up for a genetically modified cell product
• Patient >= 18 years provides voluntary written consent prior to the performance of any research related procedure. Minors (< 18 years) provide voluntary written assent with the parent/guardian signing the treatment consent prior to the performance of any research related procedure

Exclusion Criteria

• Diagnosis of acute promyelocytic leukemia (APL)
• Pregnant or breastfeeding, menstruating females of child-bearing potential must have a negative pregnancy test within 14 days of study treatment start
• Known allergy to any of study drugs or their components
• Clinically significant cardiovascular disease including any of the following: myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association grade 2 or higher or cardiac ejection fraction < 40%
• Any known condition that requires systemic immunosuppressive therapy (> 5 mg prednisone daily or equivalent) during the FT538 dosing period (3 days before the 1st dose through 14 days after the last dose) excluding pre-medications – inhaled and topical steroids are permitted
• Receipt of any biological therapy, chemotherapy, or radiation therapy, except for palliative purposes, within 2 weeks prior to day 1 or five half-lives, whichever is shorter; or any investigational therapy within 28 days prior to the to the first dose of daratumumab. Maintenance hydroxyurea for blast control up to the initiation of lympho-conditioning is permitted
• Known active central nervous system (CNS) involvement or treated CNS disease that has not cleared. If prior disease related CNS involvement must have completed effective treatment of their CNS disease at least 2 months prior to day 1 with no clinical evidence of disease
• Non-malignant CNS disease such as epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment
• Clinically significant untreated/uncontrolled infection
• Live vaccine < 6 weeks prior to start of lympho-conditioning
• Known seropositive for human immunodeficiency virus (HIV) or known active hepatitis B or C infection with detectable viral load by polymerase chain reaction (PCR)
• Prior solid organ transplant
• Allogeneic hematopoietic stem cell transplantation (HSCT) within previous 90 days
• Active graft-versus-host-disease (GvHD) requiring systemic immunosuppression within 14 days prior to enrollment
• Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to the participant