Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)

NCT04107727 | Completed Phase 2

• 1 other identifier: QUIWI
• Study Type: interventional
• Target: 273
• Locations: 1 country
• Sites: 45

Brief Summary

Randomized phase II trial to compare the efficacy and safety of standard chemotherapy plus quizartinib versus standard chemotherapy plus placebo in adult patients with newly diagnosed FLT3 wild-type Acute Myeloid Leukemia

Conditions

Acute Myeloid Leukemia

Keywords

Quizartinib

Outcome Measures

Primary Outcomes (1)

• Event-free survival rate

  Time from randomization to the date of the occurrence of any of the following events: CR/CRi after 1 or 2 induction cycles, death in CR/CRi or relapse, whichever occurs the first

  Through study completion, an average of 5 years

Secondary Outcomes (6)

• Maximum dose tolerated (MDT) and recommended phase 2 dose (Safety run-in phase)

  At the end of Cycle 1 of Induction and up to 59 days (Safety run-in phase)

• Composite Complete Remission (CR/CRi) with minimal residual disease (MRD) negativity

  Through study completion, an average of 5 years

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Through study completion, an average of 5 years

• Disease-free survival

  Through study completion, an average of 5 years

• Overall survival

  Through study completion, an average of 5 years

Study Arms (2)

Quizartinib

EXPERIMENTAL

Induction: Cytarabine continuous IV infusion 200 mg/m2 (days 1-7), Idarubicin IV infusion 12 mg/m2 (days 1-3), oral quizartinib (dose defined in safety run-in phase) 14 days (8-21) (dose will be halved with strong CYP3A inhibitor), up to 2 cycles of 35 days. Consolidation: Cytarabine IV infusion 1,5-3 g/m2 (days 1, 3, 5), oral quizartinib (dose defined in safety run-in phase) 14 days (6-19) (dose will be halved with strong CYP3A inhibitor), up to 4 cycles of 35 days. Maintenance: oral quizartinib 60mg/day (dose will be halved with strong CYP3A inhibitor), up to 12 cycles of 28 days

Drug: Quizartinib; Drug: Cytarabine; Drug: Idarubicin

Placebo

PLACEBO COMPARATOR

Induction: Cytarabine continuous IV infusion 200 mg/m2 (days 1-7), Idarubicin IV infusion 12 mg/m2 (days 1-3), oral placebo (dose defined in safety run-in phase) 14 days (8-21) (dose will be halved with strong CYP3A inhibitor), up to 2 cycles of 35 days. Consolidation: Cytarabine IV infusion 1,5-3 g/m2 (days 1, 3, 5), oral placebo (dose defined in safety run-in phase) 14 days (6-19) (dose will be halved with strong CYP3A inhibitor), up to 4 cycles of 35 days. Maintenance: oral placebo 60mg/day (dose will be halved with strong CYP3A inhibitor), up to 12 cycles of 28 days.

Drug: Placebo oral tablet; Drug: Cytarabine; Drug: Idarubicin

Interventions

Quizartinib DRUG

Induction: oral quizartinib (dose defined in safety run-in phase) 14 days (8-21) (dose will be halved with strong CYP3A inhibitor), up to 2 cycles of 35 days. Consolidation: oral quizartinib (dose defined in safety run-in phase) 14 days (6-19) (dose will be halved with strong CYP3A inhibitor), up to 4 cycles of 35 days. Maintenance: oral quizartinib 60mg/day (dose will be halved with strong CYP3A inhibitor), up to 12 cycles of 28 days.

Quizartinib

Placebo oral tablet DRUG

Induction: oral placebo (dose defined in safety run-in phase) 14 days (8-21) (dose will be halved with strong CYP3A inhibitor), up to 2 cycles of 35 days. Consolidation: oral placebo (dose defined in safety run-in phase) 14 days (6-19) (dose will be halved with strong CYP3A inhibitor), up to 4 cycles of 35 days. Maintenance: oral placebo 60mg/day (dose will be halved with strong CYP3A inhibitor), up to 12 cycles of 28 days.

Placebo

Cytarabine DRUG

Induction: Cytarabine continuous IV infusion, 200 mg/m2 (days 1-7), up to 2 cycles of 35 days. Consolidation: Cytarabine IV infusion, 1,5-3 g/m2 (days 1, 3, 5), up to 4 cycles of 35 days.

Placebo; Quizartinib

Idarubicin DRUG

Induction: Idarubicin IV infusion 12 mg/m2 (days 1-3), up to 2 cycles of 35 days.

Placebo; Quizartinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent before the first screening procedure. The patient and the investigator must sign informed consent form.
• Diagnosis of untreated AML (according to the World Health Organization (WHO) 2008/2016 definition)
• Age ≥ 18 and ≤70 years old at the time of screening
• Non-FLT3-ITD (allelic ratio \<0.03) at diagnosis
• Considered eligible to receive intensive chemotherapy as per investigator judgment
• Eastern Cooperative Oncology Group (ECOG) 0-2
• No contraindications for quizartinib
• The subject is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol
• No severe organ function abnormalities
• Not included in other first-line trials
• Cardiac ejection fraction ≥ 45% assessed by echocardiography or multiple-gated acquisition (MUGA).
• Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception upon enrollment, during the treatment period and for 3 months following the last dose of investigational drug or cytarabine, whichever is later
• Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment, during the treatment period, and for 3 months following the last dose of investigational drug or cytarabine, whichever is later
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Patients with a genetic diagnosis of acute promyelocytic leukemia
• Age \<18 years or \>70 years
• ECOG performance status of 3 or 4
• Prior treatment for AML, except for the following allowances:
• c) Leukapheresis d) Treatment for hyperleukocytosis with hydroxyurea
• Blastic phase of bcr/abl chronic myeloid leukemia.
• Presence of an associated active and/or uncontrolled malignancy:
• \- Patients with another neoplastic disease, for whom the Investigator has a clinical suspicion of active disease at the time of enrollment. Note: Patients with adequately treated early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia are eligible for this study. Hormonal or adjuvant therapies will be allowed for breast cancer or prostate cancer as long as they are on a stable dose for at least 2 weeks before the first dose.
• Known active and not controlled hepatitis B or hepatitis C infection. In the event of a positive viral load, please consult with the Sponsor
• Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
• Serum creatinine ≥ 250 μmol/l (≥ 2.5 mg/dL) (unless it is attributable to AML activity)
• Bilirubin, alkaline phosphatase, or Serum glutamic oxaloacetic transaminase (SGOT) \> 3 times the normal upper limit (unless it is attributable to AML activity)
• Uncontrolled or significant cardiovascular disease, including any of the following:
• Symptomatic bradycardia of fewer than 50 beats per minute, unless the subject has a pacemaker;
• QT Comparison of Fridericia's (QTcF) \>450 msec at Screening. Note: QTcF will be derived from the mean of triplicate readings;

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Dynamic Science S.L.: collaborator
• Daiichi Sankyo: collaborator

Study Sites (45)

Complejo Hospitalario Universitario de A Coruña

Santiago de Compostela, A Coruña, 15706, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital General Univesitario de Castellón

Castellon, Castellón, 12004, Spain

Location

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Las Palmas, 35020, Spain

Location

Hospital Universitario Quirón Salud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital General Universitario Santa Lucía

Cartagena, Murcia, 30200, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36312, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital Universitario de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Universitario de Galdakao

Galdakao, Vizcaya, 48960, Spain

Location

Complejo Hospitalario de Albacete

Albacete, 02006, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitari Vall Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario de Burgos

Burgos, 09006, Spain

Location

Hospital Puerta del Mar

Cadiz, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Complejo Hospitalario Regional Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, 21005, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Complejo Hospitalario Lucus Augusti

Lugo, 27003, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Regional Universitario Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33006, Spain

Location

Complejo Universitario de Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, 36071, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Complejo Hospitalario Regional Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Nuestra Señora del Prado

Talavera de la Reina, Spain

Location

Complejo Hospitalario de Toledo

Toledo, 45004, Spain

Location

Hospital Clínico Universitario Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Dr. Peset Aleixandre

Valencia, 46017, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47003, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Álava, 01009, Spain

Location

Related Publications (1)

• Montesinos P, Rodriguez-Veiga R, Bergua JM, Algarra Algarra JL, Botella C, Rodriguez-Arboli E, Bernal T, Tormo M, Calbacho M, Salamero O, Serrano J, Noriega V, Lopez-Lopez JA, Vives S, Lopez-Lorenzo JL, Colorado M, Vidriales MB, Garcia Boyero R, Olave MT, Herrera Puente P, Arce O, Barrios M, Jose Sayas M, Polo M, Gomez-Roncero MI, Barragan E, Ayala R, Chillon C, Calasanz MJ, Paiva B, Boluda B, Casas-Aviles I, Lloret-Madrid P, Sanchez MJ, Rodriguez-Medina C, Cuevas L, Raposo-Puglia JA, Mateos MC, Olivares M, Martinez-Chamorro C, Alonso N, Suarez S, Sanchez-Vadillo I, Sole Rodriguez M, Gonzalez BJ, Martinez-Frances A, Cuello R, Fernandez A, Martinez-Cuadron D, Labrador J; PETHEMA group; PETHEMA Group. Quizartinib for Newly Diagnosed FLT3-Internal Tandem Duplication-Negative AML: The Randomized, Double-Blind, Placebo-Controlled, Phase II QUIWI Study. J Clin Oncol. 2026 Jan;44(1):42-53. doi: 10.1200/JCO-25-01841. Epub 2025 Oct 13.

  PMID: 41082703 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

quizartinib; Cytarabine; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Pau Montesinos

  Hospital Universitari i Politecnic La Fe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be randomized into 1 of the 2 treatment groups (quizartinib or placebo) in a 2:1 ratio. The randomization will be stratified by age (\<60 vs. ≥60 years old) at the time of diagnosis of AML. Neither the subjects nor any of the Investigators, Sponsor, or contract research organizations (CROs) will be aware of the treatments received. An independent biostatistician, not otherwise part of the study team, will generate the randomization schedule.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Safety run-in phase: multicenter, prospective, open-label. Phase II: multicenter, prospective, randomized, placebo-controlled, double-blinded

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: September 27, 2019
• Study Start: September 5, 2019
• Primary Completion: October 3, 2024
• Study Completion: January 24, 2025
• Last Updated: March 24, 2026

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (45)