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

Phase 3

Recruiting

• Conditions: Leukemia
• Interventions: Drug: Quizartinib; Drug: Placebo; Drug: Chemotherapy

• Registration Number: NCT06578247
• Lead Sponsor: Daiichi Sankyo

Brief Summary

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).

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.

Study Timeline

• Study First Submitted: 2024-08-14
• Study First Submitted QC: 2024-08-27
• Study First Posted: 2024-08-29
• Study Start: 2024-11-19
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-18
• Primary Completion: 2030-06-26
• Study Completion: 2030-06-26

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 700

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

Key

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Quizartinib + Chemotherapy	Quizartinib	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)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance	Quizartinib	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)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance	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 placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
Arm A: Quizartinib + Chemotherapy	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)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance	Placebo	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)
Arm B: Placebo + Chemotherapy	Placebo	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)
Arm B: Placebo + Chemotherapy	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)

Primary Outcome Measures

Name	Time	Method
Overall Survival (Arm A vs Arm B)	Date of first patient randomized to the target number of deaths reached, up to approximately 42 months	Overall survival (OS) is defined as the time from randomization until death from any cause.

Secondary Outcome Measures

Name	Time	Method
Event-free survival (Arm A vs. Arm B)	Date of randomization up to approximately 42 months	Event-free survival (EFS) is defined as failure to achieve Complete Remission (CR) (as assessed by Independent Review Committee (IRC)) at end of induction, relapse after CR, or death due to any cause, whichever occurs first
Duration of complete response (Arm A vs. Arm B)	Date of randomization up to approximately 42 months	Duration of complete response (DoCR) is defined as time from the first documented CR until documented relapse or death due to any cause, whichever comes first
Relapse-free survival (Arm A vs. Arm B)	Date of randomization up to approximately 42 months	Relapse-free survival (RFS) is defined as time from randomization, for participants who achieve CR in the Induction Phase, until relapse or death due to any cause, whichever comes first
Complete remission rate (Arm A vs. Arm B)	At end of Induction Phase, up to approximately 120 days	Complete remission rate (CR) is defined as proportion of of participants who achieved a CR
Complete remission rate with minimal or measurable residual disease (Arm A vs. Arm B)	At end of Induction Phase (Cycle 1 or Cycles 1 and 2) and at the end of 2 cycles (2 cycles of induction or 1 cycle induction and 1 cycle consolidation)(1 Induction cycle is up to 60 days, 1 Consolidation cycle is 28 days), up to approximately 120 days	Proportion of participants achieving CR with minimal or measurable residual disease (MRD) negativity
Number of Participants With Treatment-emergent Adverse Events (Arm A vs. Arm B)	Date of first dose up to 30 days after last dose, up to approximately 42 months	Treatment-emergent adverse events (TEAE) are defined as those AEs with start or worsening date during the on-treatment period (from the first dose date of quizartinib/placebo to 30 days after the last dose date of quizartinib/placebo).

Trial Locations

Locations (265)

City of Hope Phoenix; 🇺🇸 Goodyear, Arizona, United States

Mayo Clinic - Phoenix; 🇺🇸 Phoenix, Arizona, United States

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

Ucsf - School of Medicine; 🇺🇸 San Francisco, California, United States

Stanford University School of Medicine- Parent; 🇺🇸 Stanford, California, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Mayo Clinic Hospital; 🇺🇸 Jacksonville, Florida, United States

Florida Hospital Cancer Institute - Kissimmee; 🇺🇸 Kissimmee, Florida, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

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