Quizartinib in Combination With FLAG-IDA for Relapsed or Refractory Acute Myeloid Leukemia (FLAG-QUIDA): A PETHEMA Phase I-II Trial.

Quizartinib is a tyrosine kinase inhibitor with single agent activity in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and has demonstrated efficacy in first-line therapy when combined with intensive chemotherapy in both FLT3 ITD-negative and positive AML. The FLAG-QUIDA trial was a multicenter phase 1/2 study of quizartinib combined with FLAG-IDA in adult patients with first R/R AML. The primary objectives were to determine the recommended phase 2 dose (RP2D) in phase 1 and to establish the complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates in phase 2. Nine patients were included in phase 1 and 52 in phase 2. Eighteen out of 61 (30%) patients were FLT3-ITD-positive. The RP2D of quizartinib was established at 60 mg/day for 14 days per 28-day cycle. Overall, the CR/CRi rate was 56% (n = 34), and the CR/CRi plus morphologic leukemia free state (MLFS) rate was 66% (n = 40), without differences across genetic subgroups. Measurable residual disease negativity was achieved in 38% (n = 13) of CR/CRi patients. Thirty-one patients (51%) were bridged to allogeneic stem cell transplantation after FLAG-QUIDA, 28 in CR/CRi and 3 in MLFS. Median relapse-free survival was 17 months as compared to 7.6 months in a cohort of matched patients treated with FLAG-IDA without quizartinib (p = 0.028), and median overall survival was 15.8 months in the FLAG-QUIDA cohort and 8.6 months in the matched cohort (p = 0.09). No safety concerns were raised. FLAG-IDA with quizartinib demonstrated promising efficacy in R/R AML, supporting future investigations. Trial Registration: EudraCT number: 2019-001976-12; ClinicalTrials.gov identifier: NCT04112589.