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NCT02310321

A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.

Completed Phase 1, PHASE2 Results posted Last updated 2 September 2025
What this trial tests

Phase 1, PHASE2 trial testing Gilteritinib in Acute Myeloid Leukemia in 97 participants. Completed in 9 July 2024.

Timeline
26 February 2015
Primary endpoint
25 August 2021
9 July 2024

Quick facts

Lead sponsorAstellas Pharma Inc
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment97
Start date26 February 2015
Primary completion25 August 2021
Estimated completion9 July 2024
Sites55 locations across Taiwan, Japan, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Astellas Pharma Inc — full company profile →

Who can join

Adults 18 to 69, any sex, with Acute Myeloid Leukemia or FLT3-mutated Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1 Part: Maximum Tolerated Dose (MTD) of Gilteritinib Primary · Day 1 up to the end of Induction period cycle 1 (up to 42 days)

The MTD was defined as the highest dose of gilteritinib at which the posterior mean of the DLT incidence during Cycle 1 of induction therapy was estimated to be closest to 33%.

GroupValue95% CI
Phase 1: Dose Evaluation (DEv)NA
Phase 1 Part: Recommended Expansion Dose (RED) of Gilteritinib Primary · Day 1 up to the end of Induction period cycle 1 (up to 42 days)

RED was the recommended dose used in Phase 2 of the study that was decided by the sponsor's responsible person by comprehensively assessing the data obtained from the study.

GroupValue95% CI
Phase 1: Dose Evaluation (DEv)120
Phase 1 Part: Number of Participants With Dose Limiting Toxicities (DLTs) of Gilteritinib Primary · Day 1 up to the end of Consolidation Cycle 1 (approximately up to 4 months)

DLTs were defined as: Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions: * Anorexia or fatigue * Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset. * Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset, fever with neutropenia, with or without infection, infection * Grade 4 peripheral

GroupValue95% CI
Phase 1: Dose Evaluation (DEv)0
Phase 1: Dose Expansion (DEx)1
Phase 1 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Primary · From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.1 years)

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 included both serious and non-serious AEs. TEAE for Phase 1 was defined as an AE observed after the date of first dose until 30 days after the last dose.

GroupValue95% CI
Phase 1: Dose Evaluation (DEv)3
Phase 1: Dose Expansion (DEx)10
Phase 2 Part: Complete Remission (CR) Rate: Induction Period Primary · From the date of first dose up to the start of Consolidation (approximately up to 4 months)

Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm3 and platelet count of ≥ 100,000/mm3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%.

GroupValue95% CI
Phase 2: FLT3-mutated AML5040.4 – 59.6
Phase 1 Part: Maximum Concentration (Cmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Cmax was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Induction Period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)246± 154
Phase 1: Dose Expansion (DEx)132± 27.5
Consolidation period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)133± NA
Phase 1: Dose Expansion (DEx)73.5± 17.5
Phase 1 Part: Time to Attain Cmax (Tmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Tmax was derived from the PK samples collected.

Induction period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)3.933.82 – 6.13
Phase 1: Dose Expansion (DEx)5.773.83 – 9.77
Consolidation period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)2.941.85 – 4.03
Phase 1: Dose Expansion (DEx)4.323.90 – 9.70
Phase 1 Part: Area Under Plasma Concentration-time Curve From Time 0 to 24 (AUC24) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

AUC24 was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Induction period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)3880± 2530
Phase 1: Dose Expansion (DEx)2210± 567
Consolidation period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)2110± NA
Phase 1: Dose Expansion (DEx)1160± 204
Phase 1 Part: Area Under The Concentration-Time Curve From The Time Zero to The Last Measurable Concentration (AUClast) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

AUClast was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Induction period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)3830± 2520
Phase 1: Dose Expansion (DEx)2190± 552
Consolidation period
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)2090± NA
Phase 1: Dose Expansion (DEx)1150± 202
Phase 1 Part: Plasma Trough Concentration (Ctrough) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period: Pre-dose on Cycle 1 Day 8, 11, and 17 Consolidation period: Pre-dose on Cycle 1 Day 6 and 15

Ctrough is the plasma concentration prior to drug administration. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Induction period: Cycle 1 day 8
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)245± 144
Phase 1: Dose Expansion (DEx)245± 77.7
Induction period: Cycle 1 day 11
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)283± 183
Phase 1: Dose Expansion (DEx)417± 203
Induction period: Cycle 1 day 17
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)393± 252
Phase 1: Dose Expansion (DEx)455± 143
Consolidation period: Cycle 1 day 6
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)194± NA
Phase 1: Dose Expansion (DEx)159± 12.1
Consolidation period: Cycle 1 day 15
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)285± NA
Phase 1: Dose Expansion (DEx)171± 154
Phase 1 Part: Plasma Trough Concentration of Cytarabine Concomitant With Gilteritinib With Induction and Consolidation Period Secondary · Induction period: Predose on Cycle 1 Day 1, 3, and 8 Consolidation period: Predose on Cycle 1 Day 2 and 6

Ctrough is the plasma concentration prior to drug administration. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Induction period: Cycle 1 Day 1
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)0± NA
Phase 1: Dose Expansion (DEx)0± NA
Induction period: Cycle 1 Day 3
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)34.9± 14.5
Phase 1: Dose Expansion (DEx)210± 417
Induction period: Cycle 1 Day 8
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)58.8± 8.67
Phase 1: Dose Expansion (DEx)110± 107
Consolidation period: Cycle 1 Day 2
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)4.87± NA
Phase 1: Dose Expansion (DEx)9.39± 2.19
Consolidation period: Cycle 1 Day 6
GroupValue95% CI
Phase 1: Dose Evaluation (DEv)7.09± NA
Phase 1: Dose Expansion (DEx)11.8± 1.91
Phase 2 Part: Plasma Trough Concentration of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy Secondary · Induction period : Predose on Cycle 1 Day 15 and 21 Consolidation period: Predose on Cycle 1 Day 8 and 15

Ctrough is the plasma concentration prior to drug administration.

Induction Period: Cycle 1 Day 15
GroupValue95% CI
Phase 2: FLT3-mutated AML522± 331
Induction Period: Cycle 1 Day 21
GroupValue95% CI
Phase 2: FLT3-mutated AML647± 518
Consolidation Period: Cycle 1 Day 8
GroupValue95% CI
Phase 2: FLT3-mutated AML244± 152
Consolidation Period: Cycle 1 Day 15
GroupValue95% CI
Phase 2: FLT3-mutated AML375± 249

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events: Phase 1: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.1 years) Phase 2: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.4 years) All-cause mortality: From randomization up to approximately 9.4 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1: Dose Evaluation (DEv)
Serious: 2/3 (67%)
Deaths: 0/3
Phase 1: Dose Expansion (DEx)
Serious: 1/10 (10%)
Deaths: 0/10
Phase 2: FLT3-mutated AML
Serious: 45/84 (54%)
Deaths: 25/84

Serious adverse events (56 terms)

ReactionSystemPhase 1: Dose Evaluation (…Phase 1: Dose Expansion (D…Phase 2: FLT3-mutated AML
PneumoniaInfections and infestations
SepsisInfections and infestations
Hepatic function abnormalHepatobiliary disorders
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Cardiac failureCardiac disorders
Septic shockInfections and infestations
Drug-induced liver injuryHepatobiliary disorders
Alanine aminotransferase increasedInvestigations
Chronic graft versus host diseaseImmune system disorders
Pneumonia fungalInfections and infestations
Renal impairmentRenal and urinary disorders
Atrial fibrillationCardiac disorders
Myocardial infarctionCardiac disorders
Stress cardiomyopathyCardiac disorders
GastritisGastrointestinal disorders
Acute graft versus host diseaseImmune system disorders
Graft versus host diseaseImmune system disorders
Abdominal abscessInfections and infestations
AppendicitisInfections and infestations
Bacterial sepsisInfections and infestations
Brain abscessInfections and infestations
DiverticulitisInfections and infestations
Klebsiella sepsisInfections and infestations
Liver abscessInfections and infestations
Other adverse events (110 terms — click to expand)

ReactionSystemPhase 1: Dose Evaluation (…Phase 1: Dose Expansion (D…Phase 2: FLT3-mutated AML
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Platelet count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
Neutrophil count decreasedInvestigations
StomatitisGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
HeadacheNervous system disorders
BacteraemiaInfections and infestations
VomitingGastrointestinal disorders
InsomniaPsychiatric disorders
White blood cell count decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
PneumoniaInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
Allergic transfusion reactionInjury, poisoning and procedural complications
HypophosphataemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Drug eruptionSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
UrticariaSkin and subcutaneous tissue disorders
HypertensionVascular disorders
FolliculitisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
HypoalbuminaemiaMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Hepatic function abnormalHepatobiliary disorders
MyalgiaMusculoskeletal and connective tissue disorders
Graft versus host diseaseImmune system disorders
NasopharyngitisInfections and infestations

Most-reported serious reactions: Pneumonia, Sepsis, Hepatic function abnormal, Febrile neutropenia, Pyrexia, Cardiac failure, Septic shock, Drug-induced liver injury.

Data from ClinicalTrials.gov NCT02310321 adverse events section.

Sponsor's own description

The purpose of phase 1 part in this study was to determine the maximum tolerated dose (MTD) and/or recommended expansion dose (RED) of ASP2215 concomitant with cytarabine/idarubicin as induction chemotherapy based on the status of the onset of dose-limiting toxicity (DLT) in newly diagnosed Acute Myeloid Leukemia (AML) subjects. Phase 1 part also evaluated safety and tolerability and characterized the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluated the PK parameters of cytarabine concomitant with ASP2215. The purpose of phase 2 part was to evaluate efficacy of ASP2215 in combination with induction therapy. Phase 2 cohort also evaluated safety and characterized the PK parameters of ASP2215 in combination with induction and consolidation therapy followed by maintenance therapy in newly diagnosed FLT3-mutated AML subjects.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.
    Carter JL, Hege K, Yang J, Kalpage HA, et al · · 2020 · cited 148× · PMID 33335095 · DOI 10.1038/s41392-020-00361-x
  2. A review of FLT3 inhibitors in acute myeloid leukemia.
    Zhao JC, Agarwal S, Ahmad H, Amin K, et al · · 2022 · cited 137× · PMID 34774343 · DOI 10.1016/j.blre.2021.100905
  3. Mechanisms Underlying Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.
    Eguchi M, Minami Y, Kuzume A, Chi S. · · 2020 · cited 54× · PMID 32722298 · DOI 10.3390/biomedicines8080245
  4. Midostaurin: an emerging treatment for acute myeloid leukemia patients.
    Gallogly MM, Lazarus HM. · · 2016 · cited 43× · PMID 27186148 · DOI 10.2147/jbm.s100283
  5. Overcoming Resistance to FLT3 Inhibitors in the Treatment of <i>FLT3</i>-Mutated AML.
    Lam SSY, Leung AYH. · · 2020 · cited 38× · PMID 32102366 · DOI 10.3390/ijms21041537
  6. Midostaurin In Acute Myeloid Leukemia: An Evidence-Based Review And Patient Selection.
    Abbas HA, Alfayez M, Kadia T, Ravandi-Kashani F, et al · · 2019 · cited 23× · PMID 31632141 · DOI 10.2147/cmar.s177894
  7. Gilteritinib in the treatment of relapsed and refractory acute myeloid leukemia with a FLT3 mutation.
    Chew S, Mackey MC, Jabbour E. · · 2020 · cited 11× · PMID 32547718 · DOI 10.1177/2040620720930614
  8. AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.
    Vandewalle N, De Beule N, De Becker A, De Bruyne E, et al · · 2024 · cited 7× · PMID 39367387 · DOI 10.1186/s40164-024-00566-8

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