AML-256 A Phase 1 Study of Gilteritinib in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Final Study Results

Keith W. Pratz, Mohamad Cherry, Nikolai A. Podoltsev, Jessica K. Altman, Alexander E. Perl, Brenda W. Cooper, Joseph G. Jurcic, Tara L. Lin, Gary J. Schiller, Ruishan Wu, Jason E. Hill, Stanley C. Gill, Angela James, Elizabeth Shima Rich, Nahla Hasabou, Mark J. Levis

Research output: Contribution to journalArticlepeer-review


Context: Gilteritinib, an oral FLT3 inhibitor, demonstrated antileukemic responses in patients with FLT3mut+ relapsed/refractory AML. Objective: Present final data from a phase 1 study of once-daily gilteritinib plus intensive chemotherapy in newly diagnosed (ND) AML. Design: This 4-part, open-label study (NCT02236013) assessed gilteritinib dose/schedule and effects of alternative anthracycline treatment. Intervention: Gilteritinib plus 7+3 induction with idarubicin or daunorubicin, plus ≤3 cycles of high-dose cytarabine and gilteritinib consolidation, and 2 years of single-agent gilteritinib maintenance treatment post consolidation or transplant. Patients: Adults with ND AML; FLT3 mutation not required for enrollment (known core binding factor fusions excluded). Main Outcome Measures: Safety, tolerability, PK, antileukemic effects. Results: Eighty patients were allocated to gilteritinib (safety analysis set, n=78 [age 23–77 y]; FLT3mut+, n=44 [FLT3-ITD, n=33]). Median follow-up was 37.7 months. On-study HSCT was performed in 27/80 (33.8%) patients (FLT3mut+, 26/44 [59.1%]). Dose-limiting toxicities occurred in 15/78 (19.2%) patients (200-mg/d cohort: neutropenia, n=1; neutropenic colitis, n=1). Maximum tolerated dose was 120 mg/d. Across the study, AEs led to gilteritinib discontinuation in 24.4% of patients. At end-of-treatment, composite complete remission (CRc: complete remission [CR] + CR with incomplete hematologic recovery [CRi] + CR with incomplete platelet recovery [CRp]), CR, CRi, and CRp rates were 79.7%, 54.4%, 21.5%, and 3.8%, respectively, in the overall population and 90.9%, 70.5%, 13.6%, and 6.8% among FLT3mut+ patients. In the overall (n=79) and FLT3mut+ populations (n=44), 60-day mortality rates were 1.3% and 0%, respectively, and median (95% CI) disease-free survival was 15.1 (9.5, 31.9) and 15.1 (4.9, 31.9) months. In the overall (n=69) and FLT3mut+ populations (n=41) receiving ≥80 mg/d, median (95% CI) OS was 38.6 (21.7, NE) and 45.9 (30.8, NE) months, respectively, and the estimated 3-year OS rate was 56.0% and 60.1%. Anthracycline choice did not substantially impact CRc rate or toxicity. In patients who achieved CRc with gilteritinib ≥120 mg/d, mutational clearance of FLT3-ITD (summed FLT3 ITD:wildtype signal ratio ≤10–4) after consolidation was 84.6% (11/13). Conclusions: Gilteritinib plus induction and consolidation chemotherapy was well tolerated and resulted in CR, FLT3-ITD clearance, and long-term survival in patients with ND FLT3mut+ AML, supporting ongoing randomized trials testing this approach against current standards.

Original languageEnglish (US)
Pages (from-to)S230
JournalClinical Lymphoma, Myeloma and Leukemia
StatePublished - Oct 2022


  • AML
  • FLT3, gilteritinib
  • Phase I
  • acute myeloid leukemia
  • adverse events
  • clinical response

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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