A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy

EFS: time from the date of randomization until the date of documented relapse from Complete Remission (CR), treatment failure(failing to achieve CR within 6 cycles of treatment) or death from any cause, whichever occurred first. CR: bone marrow(BM) regenerating normal hematopoietic cells, morphologically leukemia-free state, absolute neutrophil count (ANC) ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being red blood cell (RBC) and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. Relapse: reappearance of leukemic blasts >2% in the peripheral blood/≥ 5% myeloblasts in the BM unattributable to any other cause/new/reappearance of extramedullary leukemia.

Best response for a participant was defined as the best measured response (in the order of CR, CR with Incomplete Platelet Recovery (CRp), CR with Incomplete Hematologic Recovery (CRi), and treatment failure) from all post-baseline visits. CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. CRp: achieved CR except incomplete platelet recovery (< 100 × 10^9/L). CRi: achieved CR except incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence not required.

CR rate: number of participants who achieved the best response of CR divided by the number of participants in the analysis population. Participants with unknown or missing response, or who provided no information on response at the end of treatment were included in the denominator when calculating rates. CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent(1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods.

CRc rate was defined as participants with best response of (CR + CRp + CRi) divided by the number of participants in the analysis population. Participants were classified as: CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. CRp: achieved CR except incomplete platelet recovery (< 100 × 10^9/L). CRi: achieved CR except incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence not required. Percentage of participants with CRc was reported.

CRh was defined as the response at a post baseline visit as CRh having bone marrow myeloblast count < 5%, partial hematologic recovery ANC ≥ 0.5 x 10^9/L and platelets ≥ 50 x 10^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood must be ≤ 2% or missing. CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. Percentage of participants with CRh was reported.

CR/CRh rate: number of participants who achieved CR or CRh divided by the number of participants in the analysis population. CR/CRh: CR/CRh if it fulfilled criteria for CR or CRh at the visit. CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. CRh: response at a post baseline visit as CRh having bone marrow myeloblast count < 5%, partial hematologic recovery ANC ≥ 0.5 x 10^9/L and platelets ≥ 50 x 10^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood must be ≤ 2% or missing. Percentage of participants with CR/CRh was reported.

Transfusion conversion rate was defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period.

Transfusion maintenance rate was defined as the number of participants who were transfusion independent at baseline period and remained transfusion independent post-baseline period divided by the total number of participants who were transfusion independent at baseline period.

LFS: time from the date of first CRc (CR + CRp + CRi) until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CRc. CR: BM regenerating normal hematopoietic cells, morphologically leukemia-free state, ANC ≥1 × 10^9/L, platelet count ≥100 × 10^9/L, normal marrow differential with <5% myeloblast counts, missing/≤2% peripheral blood blast counts and being RBC and platelet transfusion independent (1 week without RBC and platelet transfusion prior to the disease assessment). No evidence of extramedullary leukemia and Auer rods. CRp: achieved CR except incomplete platelet recovery (< 100 × 10^9/L). CRi: achieved CR except incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence not required. CRc: fulfilled criteria for CR, CRp or CRi. Based on KM estimates.

Duration of remission included CRc, CR, CRh, CR/CRh, and response duration [CRc + PR]. Duration of CRc, CR, CRh: the time from the date of first CRc until the date of first documented relapse for participants who achieved CRc, CR, and CRh, respectively. CR/CRh: fulfilled criteria for CR or CRh at the visit. CRh: marrow blasts <5%, ANC ≥0.5×10^9/L, platelets ≥50×10^9/L, not meeting CR criteria. PR: If marrow myeloblasts between <5% and 25% and ≤2% or missing peripheral blood blast and a decrease from baseline of at least 50% in the marrow myeloblasts and no evidence of extramedullary leukemia, the response was classified as PR. If marrow myeloblasts <5% and ≤2% or missing peripheral blood blast and no evidence of extramedullary leukemia, the response was classified as PR even with Auer rods.

The BFI was a tool to assess fatigue severity and impact on daily function in cancer participants over 24 hours. It included 9 items. A global fatigue score was computed by averaging the scores of the 9 items measured on the numeric rating scale. Scores were calculated if ≥5 of 9 items were answered. A higher score indicates a higher degree of fatigue. The first 3 rate fatigue from 0 (no fatigue) to 10 (worst imaginable), with higher scores indicating worse outcomes. The remaining 6 assess how fatigue interferes with daily activities from 0 (no interference) to 10 (completely interferes). A global fatigue score (0-10) was the average of all items, with higher scores indicating worse fatigue. Overall BFI score is reported.

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE was defined as an adverse event observed after starting administration of the study drug until 30 days from the last study treatment

ECOG performance scores at each assessment time were be provided by treatment group. Negative change scores indicated an improvement and positive scores indicate a decline in performance. The grades were defined as follows:

0: Fully active, able to carry on all pre-disease performance without restriction.

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
5. Dead.