Approximately 30% of adult AML subjects are refractory to induction therapy. Furthermore, of those who achieve CR, approximately 75% will relapse. FLT3-mutated AML comprise an especially poor prognosis group.
Until now, there was no established standard for relapsed subjects with FLT3 mutations and less than 20% will achieve CR with subsequent treatment.
In phase 3 Study ADMIRAL Trial, gilteritinib has resulted in CRc in over 25% of subjects receiving 120 mg/day before on study HSCT. With this treatment, the median overall survival is at 9.3 months, furthermore, gilteritinib was well tolerated at the proposed doses. This study has been designed for R/R patients for which gilteritinib as single agent has been showed to be superior to high- and low-intensity chemotherapy (Perl, NEJM 2019, Supp Table S4) and patients included in this study will receive this treatment. Beyond high- or low-intensity chemotherapy, other options available are best supportive car or other clinical trials.
The aim of this study is to assess the efficacy and safety of the addition of oral-azacitidine to salvage treatment by gilteritinib in subjects ≥18 years of age with relapsed/refractory FLT3-mutated acute myeloid leukemia
Confirmed diagnosis of acute myeloid leukemia (AML) according to world health organization (WHO) 2016 classification
Presence of FLT3-mutation(s) at inclusion: in case of FLT3-ITD, the ITD/wt ratio must be > 0.05 ; in case of FLT3-TKD, the mutation must be at D835 or I836 position with a VAF > 5% by NGS.
Subjects must be primary refractory or relapsed (R/R) to 1st line intensive chemotherapy (ICT) for AML. Hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis.
adequate renal function as demonstrated by a creatinine clearance ≥ 50 ml/min; calculated by the Cockcroft gault formula or measured by 24-hours urine collection
None
Single group
AzaCITIDine Oral Tablet
DrugAML study treatment
Xospata
DrugR/R FLT3-mutated AML standard treatment
characterize the rate of composite complete remission (CRc) as the best response to treatment during the first 3-months treatment
the rate of composite complete remission (CRc) \[defined by addition of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with incomplete platelet recovery (CRp)\]
characterize the Incidence and relatedness of adverse events (AE) and the percent of early death, with the combination of oral-azacitidine and gilteritinib
description of toxicities according CTCAE v4.0, and death
characterize the rate of CR, rate of CRi, rate of CRp, rate of CRh
rate of complete remission (CR), rate of complete remission with incomplete hematologic recovery (CRi), rate of complete remission with incomplete platelet recovery (CRp), rate of complete remission with partial hematologic recovery (CRh)
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French Innovative Leukemia Organisation
Lead sponsor
Acute Leukemia French Association
Collaborator
