Cellectis agreed with the FDA to the following main revisions to be implemented in Phase 1 UCART123 protocols to lift the hold:
- Decrease of the cohort dose level to 6.25×104 UCART123 cells/kg;
- Decrease of the cyclophosphamide dose of the lympho-depleting regimen to 750 mg/m²/day over three days with a maximum daily dose of 1.33 grams of cyclophosphamide;
- Inclusion of specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, no organ dysfunction since eligibility screening;
- Provision to ensure that the next three patients to be treated in each protocol will be under the age of 65;
- Provision to ensure that the enrollment will be staggered across the UCART123 protocols AML123 and ABC123: at least 28 days should elapse between the enrollments of two patients across the two studies.