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NCT02984995

Phase 2 Study of Quizartinib in Participants With Acute Myeloid Leukemia (AML) FLT3 Internal Tandem Duplication (FLT3/ITD) Mutation

Completed Phase 2 Results posted Last updated 17 February 2020
What this trial tests

Phase 2 trial testing Quizartinib in Leukemia, Myeloid, Acute in 37 participants. Completed in 14 September 2018.

Timeline
8 December 2016
Primary endpoint
28 March 2018
14 September 2018

Quick facts

Lead sponsorDaiichi Sankyo Co., Ltd.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment37
Start date8 December 2016
Primary completion28 March 2018
Estimated completion14 September 2018
Sites27 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo Co., Ltd. — full company profile →

Who can join

20 and older, any sex, with Leukemia, Myeloid, Acute. 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.

Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Primary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation

The composite complete remission (CRc) rate is defined as the proportion of participants whose best response is complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]) after treatment with quizartinib.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib56.537.5 – 74.2
Initial Dose 20 mg/Day Quizartinib33.31.7 – 86.5
Total53.836.2 – 70.8
Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML

Best response is defined as the best measured response over all response assessments (complete response \[CR\], CR with incomplete platelet recovery \[CRp\], CR with incomplete hematological recovery \[CRi\], partial remission \[PR\], no response \[NR\], or Unknown) at all time points after the first dose of the study drug to the end of treatment (does not include response from any subsequent AML therapy including transplantation).

Complete response (CR)
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib0
Initial Dose 20 mg/Day Quizartinib0
Total0
Complete response with incomplete platelet (CRp)
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib1
Initial Dose 20 mg/Day Quizartinib0
Total1
Complete response with incomplete hematologic(CRi)
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib12
Initial Dose 20 mg/Day Quizartinib1
Total13
Partial remission (PR)
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib6
Initial Dose 20 mg/Day Quizartinib1
Total7
No response (NR)
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib5
Initial Dose 20 mg/Day Quizartinib1
Total6
Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib79.257.8 – 92.9
Initial Dose 20 mg/Day Quizartinib66.79.4 – 99.2
Total77.857.7 – 91.4
Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation

Duration from the date of first composite complete remission (CRc) (complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]) observed to the date of documented relapse was assessed.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib16.14.7 – 24.6
Initial Dose 20 mg/Day QuizartinibNANA – NA
Total16.14.7 – 24.6
Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 1 year

OS is defined as the time from registration (enrollment) until death from any cause.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib34.127.1 – NA
Initial Dose 20 mg/Day QuizartinibNA22.6 – NA
Total34.127.1 – NA
Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 32 weeks

Event-free survival is defined as the time from date of registration until documented refractory disease, relapse after response of composite complete remission (CRc = complete remission \[CR\], CR with incomplete platelet recovery \[CRp\], or CR with incomplete hematological recovery \[CRi\]), or death from any cause, whichever occurs first.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib12.70.1 – 24.7
Initial Dose 20 mg/Day Quizartinib0.10.1 – NA
Total12.70.1 – 24.7
Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 28 weeks

Leukemia-free survival (LFS) is the time from the first documented response of CRc until documented relapse or death from any cause. The analysis for LFS will be conditional on the participant having a documented best response of CRc.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib16.14.7 – 24.6
Initial Dose 20 mg/Day QuizartinibNANA – NA
Total16.14.7 – 24.6
Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Up to new AML treatment or 1 year post treatment

Proportion of participants who start hematopoietic stem cell transplantation (HSCT) immediately after the end of treatment with the study drug without receiving other treatment for AML, except for conditioning regiment for HSCT, was assessed.

GroupValue95% CI
Initial Dose 30 mg/Day Quizartinib37.920.7 – 57.7
Initial Dose 20 mg/Day Quizartinib33.30.8 – 90.6
Total37.521.1 – 56.3
Change in the Area Under the Plasma Concentration Time Curve (AUC) of Quizartinib and Its Active Metabolite After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Cycle 1, Days 1 and 15; Cycle 2, Day 1
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)877± 489
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)1170± 716
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)75.1± 80.6
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)560± 391
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)2610± 693
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)3970± 2610
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)430± 276
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)3120± 1300
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)2960± 749
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)9240± 6090
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)983± 389
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)6530± 2630
Change in the Maximum Plasma Concentration (Cmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Cycle 1, Days 1 and 15; Cycle 2, Day 1
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)48.1± 25.9
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)76.9± 46.8
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)3.92± 4.49
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)29.1± 20.9
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)127± 35.9
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)211± 132
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)18.9± 12.1
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)146± 60.4
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)149± 38.2
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)480± 296
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)43.7± 17.7
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)298± 118
Change in the Trough Plasma Concentration (Ctrough) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Cycle 1, Day 15
Cycle 1, Day 15; Quizartinib
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)98.2± 19.7
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)128± 92.5
Cycle 1, Day 15; Active Metabolite
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)17.8± 11.3
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)112± 47.9
Change in the Time to Reach Maximum Plasma Concentration (Tmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML Secondary · Cycle 1, Days 1 and 15; Cycle 2, Day 1
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)4.082.17 – 6.17
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)4.031.85 – 24.20
Cycle 1, Day 1; Active Metabolite (n=2,33,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)24.3324.25 – 24.42
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)24.323.93 – 24.67
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)4.084.08 – 6.25
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)3.061.42 – 6.08
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)
GroupValue95% CI
Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)4.080 – 6.25
Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)5.820.83 – 24.50
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)6.176.08 – 6.24
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)3.870 – 6.23
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)
GroupValue95% CI
Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)14.174.25 – 24.08
Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)5.650 – 24.02

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the signing of the informed consent form through 45 days after last dose of study drug up to approximately 2 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Initial Dose 30 mg/Day Quizartinib
Serious: 14/34 (41%)
Deaths: 13/34
Initial 20 mg/Day Quizartinib
Serious: 3/3 (100%)
Deaths: 1/3
Total
Serious: 17/37 (46%)
Deaths: 14/37

Serious adverse events (22 terms)

ReactionSystemInitial Dose 30 mg/Day Qui…Initial 20 mg/Day Quizarti…Total
Febrile neutropeniaBlood and lymphatic system disorders
BacteremiaInfections and infestations
SepsisInfections and infestations
CellulitisInfections and infestations
EncephalitisInfections and infestations
PneumoniaInfections and infestations
AnemiaBlood and lymphatic system disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
HematomaVascular disorders
Shock hemorrhagicVascular disorders
HemoptysisRespiratory, thoracic and mediastinal disorders
Organizing pneumoniaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Pyoderma gangrenosumSkin and subcutaneous tissue disorders
Disease progressionGeneral disorders
Non-cardiac chest painGeneral disorders
Edema peripheralGeneral disorders
Platelet count decreasedInvestigations
Other adverse events (45 terms — click to expand)

ReactionSystemInitial Dose 30 mg/Day Qui…Initial 20 mg/Day Quizarti…Total
Electrocardiogram QT prolongedInvestigations
Platelet count decreasedInvestigations
NauseaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
HypokalemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
DiarrheaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
AcarodermatitisInfections and infestations
PneumoniaInfections and infestations
DysgeusiaNervous system disorders
Peripheral sensory neuropathyNervous system disorders
ConstipationGastrointestinal disorders
StomatitisGastrointestinal disorders
UrticariaSkin and subcutaneous tissue disorders
Neck painMusculoskeletal and connective tissue disorders
EdemaGeneral disorders
Gamma-glutamyltransferase increasedInvestigations
Liver function test increasedInvestigations
FallInjury, poisoning and procedural complications
BacteremiaInfections and infestations
CellulitisInfections and infestations
Device-related infectionsInfections and infestations
NeutropeniaBlood and lymphatic system disorders
HypotensionVascular disorders
PhlebitisVascular disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
ProctalgiaGastrointestinal disorders
Liver disorderHepatobiliary disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders

Most-reported serious reactions: Febrile neutropenia, Bacteremia, Sepsis, Cellulitis, Encephalitis, Pneumonia, Anemia, Disseminated intravascular coagulation.

Data from ClinicalTrials.gov NCT02984995 adverse events section.

Sponsor's own description

This is a Phase 2, multi-center, open-label study to evaluate the efficacy, safety and pharmacokinetics of quizartinib monotherapy in Japanese subjects with FLT3-ITD positive refractory or relapsed acute myeloid leukemia.

Publications & conference data

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

  1. Recent advances in targeted therapies in acute myeloid leukemia.
    Bhansali RS, Pratz KW, Lai C. · · 2023 · cited 151× · PMID 36966300 · DOI 10.1186/s13045-023-01424-6
  2. The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.
    Pimenta DB, Varela VA, Datoguia TS, Caraciolo VB, et al · · 2021 · cited 61× · PMID 34869355 · DOI 10.3389/fcell.2021.764698
  3. Quizartinib (AC220): a promising option for acute myeloid leukemia.
    Zhou F, Ge Z, Chen B. · · 2019 · cited 48× · PMID 31114157 · DOI 10.2147/dddt.s198950
  4. Profile of Quizartinib for the Treatment of Adult Patients with Relapsed/Refractory FLT3-ITD-Positive Acute Myeloid Leukemia: Evidence to Date.
    Fletcher L, Joshi SK, Traer E. · · 2020 · cited 26× · PMID 32021432 · DOI 10.2147/cmar.s196568
  5. Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.
    Tecik M, Adan A. · · 2022 · cited 25× · PMID 36474506 · DOI 10.2147/ott.s384293
  6. Targeting FLT3 Signaling in Childhood Acute Myeloid Leukemia.
    Sexauer AN, Tasian SK. · · 2017 · cited 24× · PMID 29209600 · DOI 10.3389/fped.2017.00248
  7. Quizartinib: a potent and selective FLT3 inhibitor for the treatment of patients with FLT3-ITD-positive AML.
    Cortes J. · · 2024 · cited 18× · PMID 39538314 · DOI 10.1186/s13045-024-01617-7
  8. Efficacy and safety of quizartinib in Japanese patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia in an open-label, phase 2 study.
    Takahashi T, Usuki K, Matsue K, Ohno H, et al · · 2019 · cited 15× · PMID 31473943 · DOI 10.1007/s12185-019-02727-6

Verify or expand the search:

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02984995.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing