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: 2025-10
• Last Update Submitted: 2025-10-22
• Last Update Posted: 2025-10-24
• Primary Completion: 2030-06-26
• Study Completion: 2030-06-26

Recruitment & Eligibility

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

Inclusion Criteria

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

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 (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).

2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy.

3. Diagnosis of AML with known antecedent myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and others.

4. 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.

5. Prior treatment for AML, except for the following allowances prior to Day 1 of chemotherapy:

   1. Leukapheresis;
   2. Treatment for hyperleukocytosis with hydroxyurea;
   3. Cranial radiotherapy for central nervous system (CNS) leukostasis;
   4. Prophylactic intrathecal chemotherapy

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 time from randomization to date of failure to achieve CR 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. As assessed by Independent Review Committee.
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. As assessed by Independent Review Committee .
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. As assessed by Independent Review Committee.
Complete remission rate with minimal or measurable residual disease (Arm A vs. Arm B)	At end of Induction Phase (Cycle 2 or Cycles 1 and 2), up to approximately 120 days	Proportion of participants achieving CR with minimal or measurable residual disease (MRD) negativity. As assessed by Independent Review Committee.
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 (276)

Robert H Lurie Comprehensive Cancer Center Northwestern University; 🇺🇸 Chicago, Illinois, United States

Peggy & Charles Stephenson Oklaho; 🇺🇸 Oklahoma City, Oklahoma, United States

Hospital Erasto Gaertner - Liga Paranaense de Combate Ao Că'Ncer; 🇧🇷 Curitiba, Brazil

Hc-Ufg - Hospital Das Clă Nicas Da Universidade Federal de Goiă S; 🇧🇷 Goiânia, Brazil

Hospital de Clă Nicas de Passo Fundo; 🇧🇷 Passo Fundo, Brazil

Hospital de Clă Nicas de Porto Alegre; 🇧🇷 Porto Alegre, Brazil

Umhat  Sv. Ivan Rilskiâ , Ead; 🇧🇬 Sofia, Bulgaria

The First Affiliated Hospital of Xiâ An Jiaotong University; 🇨🇳 Xi'an, China

Chu Angers - Hă"Pital Hă"Tel Dieu; 🇫🇷 Angers, France

Chu de Bordeaux - Hă"Pital Haut-Lă Vă Que; 🇫🇷 Pessac, France

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