Study of Cell Therapies for the Treatment of Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome.

Master Protocol: The main goal of this master clinical trial study is to assesses the safety, tolerability, pharmacokinetic (PK), Pharmacodynamic (PD) in participants with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The goal of the Arm 1 study is to assess the safety, tolerability, PK, and PD of the study drugs, Antigen Receptor Complex T (ARC-T) cells and CD123-specific soluble protein antigen-receptor X-linker (SPRX002), in participants with relapsed or refractory AML or MDS. The primary objective of this study is to assess the safety profile (including any dose-limiting toxicity (DLT)), to determine recommended Phase 2 dose (RP2D) of the investigational agents when infused in participants with relapsed and refractory AML or MDS.

Key Inclusion Criteria: 1. 18 years or older 2. For AML Individuals: WHO-confirmed AML, other than APL, with no standard treatment options available (WHO AML Criteria 2016) a. Relapsed or refractory disease after at least 1 line of therapy, as defined by the following: i. Relapsed: Bone marrow blasts ≥5% following achievement of CR/Cri/MLFS ii. Refractory: Failure to achieve CR/Cri/MLFS with evidence of persistent leukemia by blood and/or bone marrow examination after any of the following: 1. Failure on at least 1 cycle of an anthracycline-based induction therapy 2. At least 1 cycle of high or intermediate dose cytarabine containing induction regimen 3. At least 2 cycles of VEN-based lower intensity therapy, e.g., with HMA, or LDAC or cladribine+LDAC 4. At least 4 cycles of HMA-based therapy without venetoclax 3.For MDS Individuals: A diagnosis of MDS and ≥10% bone marrow blasts with indication of high-risk disease defined as those having resistant or refractory disease to at least one course of therapy including hypomethylating agents (e.g., decitabine or 5-azacitidine) given at conventional dose, schedule, and duration (e.g., cycle every 28 days and for at least 4 cycles) with or without venetoclax or other agents. Failure is defined as failure to attain a response, or relapse after prior response to HMA therapy per the modified IWG criteria. 4\. Patients relapsing after allogeneic hematopoietic stem cell transplant (HSCT) \>3 months prior are eligible if they have recovered from all transplant-related toxicities and are off all immunosuppression for at least 6 weeks. 5\. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 6\. Adequate organ function, including renal and hepatic function based on last clinical assessment performed within the screening period 1. Creatinine clearance ≥50 ml/min (Cockcroft-Gault or 24-hour urine collection in cases in which Cockroft-Gault is unreliable or if preferred by physician) and not on dialysis 2. Alanine aminotransferase \