Evaluation of Two Dose Levels of Quizartinib as Maintenance in FLT3-ITD (+) Acute Myeloid Leukemia Patients in Complete Remission

A Phase 2, Multicenter, Randomized, Open-label Trial to Evaluate Safety and Efficacy of Two Dose Levels of Quizartinib as Maintenance for Adult Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia in Complete Remission

This clinical two-arm trial is designed to evaluate two doses of quizartinib as maintenance therapy after induction/consolidation in participants with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (+) acute myeloid leukemia (AML) in first complete remission (CR) who have not received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Leukemia
• Intervention / Treatment: Drug: Quizartinib High Dose; Drug: Quizartinib Low Dose

Detailed Description

This study also involves the Holter sub-study, which is designed to assess the impact of rapid acceleration in heart rate on the cardiac safety of quizartinib.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Contact for Trial Information; Phone Number: 908-992-6400; Email: CTRinfo_us@daiichisankyo.com

Study Locations

• Australia
  • Adelaide, Australia
    • Not yet recruiting
    • Royal Adelaide Hospital
  • Australia, Australia
    • Not yet recruiting
    • Austin Health
  • Darlinghurst, Australia
    • Not yet recruiting
    • St. Vincent's Hospital Melbourne
  • Melbourne, Australia
    • Not yet recruiting
    • The Alfred Hospital
  • Perth, Australia
    • Not yet recruiting
    • Royal Perth Hospital
  • Southport, Australia
    • Not yet recruiting
    • Gold Coast University Hospital
  • Sydney, Australia
    • Not yet recruiting
    • Westmead Hospital
• Brazil
  • Curitiba, Brazil
    • Recruiting
    • Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
  • Minas Gerai, Brazil
    • Recruiting
    • Cetus Hospital Dia Oncologia
  • Porto Alegre, Brazil
    • Recruiting
    • Hospital de Clinicas de Porto Alegre
  • Porto Alegre, Brazil
    • Recruiting
    • Irmandade da Santa Casa de Misericórdia de Porto Alegre Centro Multidisciplinar de Pesquisa
  • Rio de Janeiro, Brazil
    • Recruiting
    • INCA - Instituto Nacional de Cancer
  • San Jose Rio Preto, Brazil
    • Recruiting
    • "Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto CIP - Centro Integrado de Pesquisa"
  • São Paulo, Brazil
    • Recruiting
    • Hospital Santa Marcelina
  • São Paulo, Brazil
    • Recruiting
    • ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira
• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
  • Beijing, China
    • Not yet recruiting
    • Peking Union Medical College Hospital
  • Changchun, China
    • Recruiting
    • The First Hospital of Jilin University
  • Guangzhou, China
    • Recruiting
    • Nanfang Hospital of Southern Medical University
  • Guangzhou, China
    • Not yet recruiting
    • Sun Yat-sen University Cancer Center
  • Guangzhou, China
    • Recruiting
    • Guangdong Provincial People's Hospital
  • Hangzhou, China
    • Not yet recruiting
    • The First Affiliated Hosptial of Zhejiang University School of Medicine
  • Nanchang, China
    • Not yet recruiting
    • The First Affiliated Hospital of Nanchang University
  • Nanjing, China
    • Not yet recruiting
    • Zhong Da Hospital, Southeast University
  • Nanning, China
    • Recruiting
    • The First Affiliated Hospital of Guangxi Medical University
  • Qingdao, China
    • Not yet recruiting
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Not yet recruiting
    • Huashan Hospital, Fudan University
  • Suzhou, China
    • Not yet recruiting
    • The First Affiliated Hospital of Soochow University
  • Tianjin, China
    • Not yet recruiting
    • Hematology Hospital of the Chinese Academy of Medical Sciences
  • Wenzhou, China
    • Not yet recruiting
    • The First Affiliated Hospital of Wenzhou Medical University
  • Xi'an, China
    • Not yet recruiting
    • The First Affiliated Hospital of Jiaotong University
  • Xiamen, China
    • Not yet recruiting
    • The First Affiliated Hospital of Xiamen University
  • Xuzhou, China
    • Not yet recruiting
    • The Affiliated Hospital of Xuzhou Medical College
  • Zhengzhou, China
    • Not yet recruiting
    • The First Affiliated Hospital of Zhengzhou University
• South Korea
  • Busan, South Korea
    • Recruiting
    • Pusan National University Hospital
  • Busan, South Korea
    • Recruiting
    • Inje University Haeundae Paik Hospital
  • Daegu, South Korea
    • Not yet recruiting
    • Kyungpook National University Hospital
  • Daegu, South Korea
    • Recruiting
    • Yeungnam University Hospital
  • Goyang-si, South Korea, 10408
    • Not yet recruiting
    • National Cancer Center
  • Incheon, South Korea
    • Withdrawn
    • Gachon University Gil Medical Center
  • Jeonju, South Korea
    • Recruiting
    • Jeonbuk National University Hospital
  • Seongnam, South Korea
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 6591
    • Not yet recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea
    • Not yet recruiting
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Suwon, South Korea
    • Recruiting
    • Ajou University Hospital
  • Ulsan, South Korea
    • Recruiting
    • Ulsan University Hospital
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Not yet recruiting
      • John Hopkins School of Medicine
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Not yet recruiting
      • Umass Memorial Health Care Systems
  • New York
    • Buffalo, New York, United States, 14263
      • Withdrawn
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021-9800
      • Not yet recruiting
      • Weill Cornell
    • Valhalla, New York, United States, 10595
      • Withdrawn
      • Westchester Medical College
    • Westbury, New York, United States, 11590
      • Recruiting
      • Clinical Research Allicance
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • Not yet recruiting
      • Spoknwrd Clinical Trials Inc.
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • The University of Texas MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • The Methodist Hospital Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Adults ≥18 years of age or the minimum legal adult age (whichever is greater) on the day of signing the ICF (no upper limit of age).
2. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm based on the World Health Organization (WHO) 2008/2016 classification.
3. Participant has confirmed FLT3-ITD-positive (≥0.05 SR or ≥5% VAF) activating mutation from initial diagnosis in bone marrow or peripheral blood as determined by a local institution's validated molecular testing.

4. Participants must have confirmed, morphologically documented CR1, on the most recent BMA, based on the local laboratory results, performed within 28 days prior to C1D1 of maintenance therapy. Complete remission will be defined as <5% blasts in the bone marrow with no morphologic characteristics of acute leukemia (e.g., Auer Rods), no evidence of extramedullary disease, and no leukemic blasts in the peripheral blood.

   Complete blood count recovery is required with absolute neutrophil count of more than 1.000 × 109/L and platelets more than 100 × 109/L (IWG criteria).27

5. Participant must meet the following prior therapy requirements:

   1. Has received at least one cycle of induction therapy but no more than two to achieve CR1. The induction cycles can be the same regimen or different regimens and may contain conventional agents only (e.g., cytarabine + daunorubicin or idarubicin: "7 + 3" or "5 + 2"), or a combination with FLT3 inhibitors.
   2. Has not received more than four cycles of consolidation therapy. Regimens may contain conventional agents only.
   3. FLT3 inhibitors are permitted as part of the induction or consolidation treatment.

   Participants who received FLT3 inhibitors before enrollment in the trial will need a washout period of 14 days.

6. Able to begin the maintenance phase within 60 days of D1 of the last consolidation cycle received.
7. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2.

Key Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or BCR-ABL positive leukemia (i.e., chronic myelogenous leukemia in blast crisis); participants who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy).
2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms.

3. Prior treatment for AML, except for the following allowances:

   1. Induction and consolidation therapy, as previously described (inclusion criterion #5)
   2. Leukapheresis
   3. Hydroxyurea to treat hyperleukocytosis
   4. Cranial radiotherapy for central nervous system (CNS) leukostasis
   5. Prophylactic intrathecal chemotherapy
   6. Growth factor/cytokine support
4. Participant had received allo-HSCT as part of AML treatment.
5. Treatment with any strong or moderate CYP3A inducers within 2 weeks or 5 half-lives of randomization whichever is longer

6. Uncontrolled or significant cardiovascular disease, including the following:

   1. QTcF interval >450 ms (based on average of triplicate ECG at Screening)
   2. Diagnosed or suspected congenital long QT syndrome or known family history of congenital long QT syndrome
   3. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
   4. Participant has bradycardia of less than 50 beats per minute (bpm; as determined by central reading), unless the participant has a pacemaker
   5. History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
   6. Myocardial infarction within 6 months prior to screening
   7. Uncontrolled angina pectoris within 6 months prior to screening
   8. New York Heart Association Class 3 or 4 congestive heart failure
   9. LVEF ≤45% or institutional lower limit of normal
   10. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg despite optimal medical management)
   11. Complete left or right bundle branch block
   12. Severe aortic stenosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Participants will receive higher dose of quizartinib	Drug: Quizartinib High Dose; Participants in Arm 1 will receive oral daily higher dose of quizartinib,; Other Names: VANFLYTA®
Experimental: Arm 2; Participants will receive lower dose of quizartinib	Drug: Quizartinib Low Dose; Participants in Arm 2 will receive oral daily lower dose of quizartinib; Other Names: VANFLYTA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Treatment Emergent Adverse Events (TEAEs)	TEAEs are defined as AEs with start or worsening date during the on-treatment period (from the first dose date of trial treatment to 30 days after the last dose date of trial treatment).	From date of first dose to 30 days after last dose, up to 87 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization until death from any cause.	From date of randomization to death from any cause, up to 87 months
Relapse-free Survival (RFS)	RFS is defined as the time from randomization until documented relapse or death from any cause, whichever comes first	From date of randomization to documented relapse or death from any cause, whichever comes first, up to 87 months
TEAEs	TEAEs are defined as AEs with start or worsening date during the on-treatment period (from the first dose date of trial treatment to 30 days after the last dose date of trial treatment).	From date of first dose to 30 days after last dose, up to 87 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2025
• Primary Completion (Estimated): June 6, 2028
• Study Completion (Estimated): July 14, 2032

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: acute myeloid leukemia; leukemia; allo-HSCT; FLT3; quizartinib
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid, Acute; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; quizartinib
• Other Study ID Numbers: AC220-167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No