UCART123

P1, N=65, Recruiting, Cellectis S.A. | Trial completion date: Mar 2023 --> Dec 2024 | Trial primary completion date: Mar 2023 --> Dec 2024

AMELI-01 (NCT04106076) is a phase 1 trial evaluating the safety, tolerability, expansion, and persistence of UCART123 given at escalating dose levels after LD with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients (pts) with R/R AML.Key eligibility criteria include pts 18-65 yrs, adequate organ function, ECOG PS ≤ 1, and blasts positive for CD123 by flow cytometry. Pts must have received ≥2 cycles of chemotherapy, ≥ 1 cycle of a high/intermediate dose cytarabine containing regimen, ≥ 2 cycles of an HMA combination regimen, or prior allogeneic HSCT...Overall, these data support the safety and activity of UCART123 after FCA LD in pts with CD123+ R/R AML. Based on observed UCART123 expansion patterns and cytokine profiles, the study was amended to include a UCART123 2-dose regimen with FCA LD, and enrollment is ongoing into this arm​.

AMELI-01 (NCT04106076) is a phase 1, open-label, dose-escalation trial evaluating the safety, tolerability, expansion, and persistence of UCART123v1.2 given at escalating dose levels after LD with either fludarabine and cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients (pts) with R/R CD123+ AML...Pts must have received ≥2 cycles of chemotherapy (one with standard dose cytarabine), ≥ 1 cycle of a high/intermediate dose cytarabine containing regimen, ≥ 2 cycles of an HMA combination regimen, or prior allogeneic HSCT... Adding alemtuzumab to the FC regimen was associated with improved LD and significantly higher UCART123v1.2 cell expansion and persistence, which correlated with improved activity and safety, including one pt in the DL2 FCA arm who achieved a durable MRD-negative CR. Overall, these data support the safety and activity of UCART123v1.2 after FCA LD in pts with CD123+ R/R AML.

As safety feature, cells express RQR8 to allow elimination with Rituximab. Furthermore, UCART123 preferentially target AML over normal cells with modest toxicity to normal hematopoietic stem/progenitor cells. Together these results suggest that UCART123 represents an off-the shelf therapeutic approach for AML.

Also, the CAR is co-expressed with a suicide mechanism (RQR8), which can be activated by using rituximab...Pts receive a lymphodepletion (LD) regimen of either fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide plus alemtuzumab (FCA) starting on Day -5, followed by an infusion of UCART123 at one of 5 dose levels on Day 0...DL1 has cleared safety without DLT, and enrollment at the next dose levels are proceeding. ClinicalTrials.gov Identifier: NCT03190278