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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 May 2025 → ongoing

Decision date (initial)

2025-03-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Daiichi Sankyo, Inc.

External identifiers

EU CT number

2023-507936-20-00

ClinicalTrials.gov

NCT06578247

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic

(Arm A vs. Arm B): The primary objective of the study is 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 OS in participants with newly diagnosed FLT3-ITD negative AML

Secondary objectives 8

1. (Arm A vs. Arm B): Event-free survival (EFS)
2. (Arm A vs. Arm B): Duration of complete remission (DoCR)
3. (Arm A vs. Arm B): Relapse-free survival (RFS)
4. (Arm A vs. Arm B): Complete remission rate (CR)
5. (Arm A vs. Arm B): CR with minimal or measurable residual disease (MRD) negativity
6. (Arm A vs. Arm B): Further characterize the safety profile of quizartinib administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles
7. (Arm A vs. Arm B): Assess the pharmacokinetics (PK) of quizartinib and its metabolite (AC886)
8. (Arm C vs. Arm B): overall survival (OS)

Conditions and MedDRA coding

Acute myeloid leukemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) 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/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. 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
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. (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.
6. Required baseline local laboratory data (see details on page 165)
7. If a woman of childbearing potential, must have a negative serum pregnancy test upon entry into this trial and must be willing to use highly effective birth control upon enrollment, during the treatment period and for 7 months following the last dose of quizartinib/placebo or cytotoxic chemotherapy (i.e. anthracycline, cytarabine) whichever is later (see details on page 166)
8. Female participants must not donate, or retrieve for their own use, ova from the time of initiation of 7+3 chemotherapy and throughout the trial treatment period and for at least 7 months after the final trial drug administration.
9. If male, must be surgically sterile or willing to use highly effective birth control as well as a condom upon enrollment, during the treatment period, and for 4 months following the last dose of quizartinib/placebo, or for 6 months following the last dose of cytotoxic chemotherapy, whichever is later.
10. Male participants must not freeze or donate sperm starting at screening and throughout the trial period, and at least 4 months after the last dose of quizartinib/placebo, or for 6 months following the last dose of cytotoxic chemotherapy, whichever is later.
11. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions
12. Consolidation Phase: Achieved CR or CRi, based on local laboratory results, at the end of the Induction Phase
13. Consolidation Phase: Able to begin Consolidation Phase within 60 days of Day 1 of the last Induction cycle
14. Maintenance Phase: Confirmed <5% of blasts based on the most recent bone marrow aspirate, based on the local laboratory results, performed within 28 days prior to Cycle 1 Day 1 of maintenance therapy
15. Maintenance Phase: Absolute neutrophil count (ANC) >500/mm3 and platelet count >50,000/mm3 without platelet transfusion support within 24 hours prior to Cycle 1 Day 1 of maintenance therapy
16. Maintenance Phase: Able to begin Maintenance Phase within 60 days of Day 1 of the last Consolidation cycle received or within 180 days after allo-HSCT (ie, stable after transplant).
17. Maintenance Phase: For participants who undergo allo-HSCT: Participant does not have active acute or ≥Grade 3 graft-versus-host disease (GVHD)or severe chronic GVHD.
18. Maintenance Phase: For participants who undergo allo-HSCT: Participant has not initiated therapy for active GVHD (prophylaxis is allowed) within 21 days
19. Maintenance Phase: For participants who undergo allo-HSCT: All Grade 3 and 4 non-hematological toxicities have resolved to ≤Grade 2 (with the exception of alopecia).

Exclusion criteria 19

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) (see details on pg 167)
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 induction chemotherapy : a. Leukapheresis; b. Treatment for hyperleukocytosis with hydroxyurea; c. Cranial radiotherapy for central nervous system (CNS) leukostasis; d. Prophylactic intrathecal chemotherapy;
6. Prior treatment with quizartinib or other FLT3 inhibitors (eg, midostaurin, sorafenib).
7. Prior treatment with any investigational drug or device within 30 days prior to randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational procedures.
8. Inadequate washout period before randomization, defined as major surgery <4 weeks or ≤2 weeks for low-invasive cases (eg, colostomy).
9. Known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for participants with symptoms of CNS leukemia to rule out extramedullary CNS involvement
10. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated with no evidence of disease for at least 2 years.
11. Uncontrolled or significant cardiovascular disease (for details see page 168)
12. Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy. Note: Participants with localized fungal infections of skin or nails are eligible.
13. Known active clinically relevant liver disease (eg, active hepatitis B or active hepatitis C), based on available blood tests, liver ultrasound, or liver biopsy results. Participants who are hepatitis B surface antigen positive (HBsAg+), with hepatitis B virus (HBV) infection for more than 6 months, have an HBV DNA viral load <2000 IU/mL, have normal transaminase values at baseline, and are willing to start and maintain antiviral treatment for the duration of the trial are allowed.
14. Has active primary immunodeficiency or active human immunodeficiency virus ( HIV) infection as determined by plasma HIV RNA viral load and CD4 count. Participants with undetectable viral load or normalized CD4 count (CD4+ T-cell counts ≥350 cells/μL) and no opportunistic infection within the past 12 months will be eligible. These participants must be on established antiretroviral therapy for at least 4 weeks and have an HIV viral load <400 copies/mL prior to enrollment. Participants should be tested for HIV prior to randomization if required by local regulations or EC.
15. Uncontrolled hypothyroidism
16. History of severe hypersensitivity to any excipients in the quizartinib/placebo tablets
17. Females who are pregnant or breastfeeding
18. Otherwise considered inappropriate for the trial by the investigator including where other treatment options, such as gemtuzumab ozogamicin, are preferred according to local institutional practice.
19. Treatment with any strong or moderate CYP3A inducers within 2 weeks or 5 half-lives of randomization whichever is longer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) in participants with newly diagnosed FLT3 ITD negative AML

Secondary endpoints 8

1. (Arm A vs Arm B) Event-free survival (EFS): Time from randomization to date of failure to achieve CR (as assessed by IRC) at end of induction, relapse after CR, or death due to any cause, whichever occurs first
2. (Arm A vs Arm B) Duration of complete response (DoCR): Time from the first documented CR until documented relapse or death due to any cause, whichever comes first
3. (Arm A vs Arm B) Relapse Free Survival (RFS): Time from randomization, for participants who achieve CR in the Induction Phase, until relapse or death due to any cause, whichever comes first
4. (Arm A vs Arm B) Complete remission rate (CR): Percentage of participants who achieved a CR
5. (Arm A vs Arm B) CR with minimal or measurable residual disease (MRD) negativity: MRD negativity by NPM1, CBF, and FLT3-ITD (assessed individually in patients with NPM1 and CBF mutations present at screening and in all patients for FLT3-ITD MRD levels)
6. (Arm A vs B) Incidence of treatment-emergent adverse events (TEAEs), serious (TEAEs), AESIs, changes in vital signs, ECG, safety laboratory evaluations and physical examinations
7. Arm A vs Arm B) Plasma concentrations at each time point and PK parameters (AUC24h, Cmax, Cmin, Tmax, and accumulation ratio and parent/metabolite ratio)
8. (Arm B vs C) OS: Time from randomization to date of death due to any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 8

Locations

15 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 502 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications