Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML

Purpose

This study will compare the effects of Quizartinib versus placebo in combination with chemotherapy in participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML).

Condition

  • Leukemia

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Must be competent and able to comprehend, sign, and date an Ethics Committee (EC)- or Institutional Review Board (IRB)-approved Informed Consent Form (ICF) before performance of any trial-specific procedures or tests. - ≥18 years or the minimum legal adult age (whichever is greater) and 70 years (at Screening). - Newly diagnosed, morphologically documented primary AML based on the World Health Organization (WHO) 2016 classification (at Screening) - Eastern Cooperative Oncology Group (ECOG) performance status (at the time the participant signs their ICF) of 0-2. - Participant is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol

Exclusion Criteria

  • 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 (ie, 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). - Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms or autoimmune/rheumatologic conditions. - Diagnosis of AML secondary to myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including CMML, aCML, JMML and others. - Participants with newly diagnosed AML with FLT3-ITD mutations (FLT3-ITD [+]) present at ≥5% VAF (or ≥0.05 SR) based on a validated FLT3 mutation assay. - Prior treatment for AML, except for the following allowances: 1. Leukapheresis; 2. Treatment for hyperleukocytosis with hydroxyurea; 3. Cranial radiotherapy for central nervous system (CNS) leukostasis; 4. Prophylactic intrathecal chemotherapy; 5. Growth factor/cytokine support.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
This study has a double-blind design. Neither the participants nor any of the investigators, Sponsor, Independent Review Committee (IRC) or contract research organizations (CROs) will be aware of the treatments received. An independent biostatistician, not otherwise part of the Sponsor trial team, will generate the randomization schedule.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A: Quizartinib + Chemotherapy 		Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive quizartinib at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
  • Drug: Quizartinib
    Participants will receive quizartinib at 60 mg/day orally once daily
    Other names:
    • Test Product
  • Drug: Chemotherapy
    Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin or idarubicin).
    Other names:
    • Cytarabine, Daunorubicin or Idarubicin
    • Standard Chemotherapy
Placebo Comparator
Arm B: Placebo + Chemotherapy 		Participants will receive placebo at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
  • Drug: Placebo
    Participants will receive placebo at 60 mg/day orally once daily
    Other names:
    • Placebo Control
  • Drug: Chemotherapy
    Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin or idarubicin).
    Other names:
    • Cytarabine, Daunorubicin or Idarubicin
    • Standard Chemotherapy
Experimental
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance 		Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
  • Drug: Quizartinib
    Participants will receive quizartinib at 60 mg/day orally once daily
    Other names:
    • Test Product
  • Drug: Placebo
    Participants will receive placebo at 60 mg/day orally once daily
    Other names:
    • Placebo Control
  • Drug: Chemotherapy
    Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin or idarubicin).
    Other names:
    • Cytarabine, Daunorubicin or Idarubicin
    • Standard Chemotherapy

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40504

More Details

NCT ID
NCT06578247
Status
Recruiting
Sponsor
Daiichi Sankyo

Study Contact

Daiichi Sankyo Contact for Clinical Trial Information
908-992-6400
CTRinfo_us@daiichisankyo.com

Detailed Description

This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.