1. Phase 1a Dose Escalationand Re-initiated Dose Escalation in 3+3 design: Safety and tolerability (Time Frame - DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance) until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)): Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS
2. Phase 1a Dose Escalation and Re-initiated Dose Escalation in 3+3 design: Incidence of dose limiting toxicity (DLT) (Time Frame - DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)): DLT is defined as any adverse Event at least possible related to TM123 and/or UniCAR02-T
3. Phase 1a Dose Escalation and Re-initiated Dose Escalation in 3+3 design: Maximum tolerated dose (MTD) (Time Frame - DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)): The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.
4. Ph1b Dose Expansion: Safety and tolerability (Time Frame - Infusion period of TM123 (up to 20 days)): Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS
5. Ph1b Dose Expansion: Establishing recommended phase 2 dose (RP2D) (Time Frame - Infusion period of TM123 (up to 20 days))
6. Ph1b Dose Expansion: Response evaluation (Time Frame - Infusion period of TM123 (up to 20 days)): Complete and partial remission at any time point and durability of response
Secondary outcome:
1. Establishing recommended phase 2 dose (RP2D) (Time Frame - DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)): The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
2. Complete (CR, CRh, CRi ) and partial remission (PR) (Time Frame - until fifteen years after last UniCAR02-T administration): CR: Bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L. Level of MRD should be measured in patients achieving CR in case as suitable marker exists.
CRi: All criteria for CR except residual thrombocytopenia (platelets < 100 Gpt/L) and/or neutropenia (absolute neutrophil count < 1 Gpt/L).
PR: All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.
3. Disease stabilization (DS) (Time Frame - until fifteen years after last UniCAR02-T administration): Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR.
4. Best response rate (Time Frame - until fifteen years after last UniCAR02-T administration): The best observed response during observational period. Response states are ordered descending as follows: CR > CRi > PR > DS > refractory disease.
5. Progression free survival (PFS) (Time Frame - until fifteen years after last UniCAR02-T administration): The time from first treatment with TM123 and UniCAR02-T until disease progression or death. If no progress of death was observed during the observational period, the patient's progression free survival time will be censored on the date the patient was last seen progression-free and alive.
6. Overall survival (OS) (Time Frame - until fifteen years after last UniCAR02-T administration): The number of days between the first study drug administration and death from any cause. If death was not observed during the observational period, the patient's overall survival time will be censored on the date the patient was last seen alive.
7. Toxicity and efficacy in repeated cycles of TM123 administration (Time Frame - duration of consolidation cycle treatment): Patients who tolerate TM123 and UniCAR02-T without DLT and achieve a clinical benefit are candidates for consolidation cycles
