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Acute Myeloid LeukemiaPhase 2NCT04107727

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)

A Phase 2 study testing Quizartinib, Cytarabine and Idarubicin in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 45 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Quizartinib, Cytarabine and Idarubicin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
273 participants
Where
45 sitesSpain
Study dates
5 Sep 2019to 24 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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:
  • Leukapheresis d) Treatment for hyperleukocytosis with hydroxyurea
  • Blastic phase of bcr/abl chronic myeloid leukemia.
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  • 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)
  • Presence of any severe psychiatric disease or physical condition that, according to the physician´s criteria, contraindicates the inclusion of the patient into the clinical trial
  • 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;
  • Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
  • Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥ 110 mmHg;
  • History of clinically relevant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes)
  • History of a second (Mobitz II) or third-degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker)
  • An ejection fraction <45%
  • History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening
  • History of New York Heart Association Class 3 or 4 heart failure
  • Right bundle branch and left anterior hemiblock (bifascicular block), complete left bundle branch block
  • History of hypersensitivity to any excipients in the quizartinib/placebo tablets
  • Females who are pregnant or breastfeeding
  • Any patients with known significant impairment in gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of quizartinib.
  • Active acute or chronic Graft-Versus-Host-Disease (GVHD) requiring prednisone >10 mg or equivalent corticosteroid daily.

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

Spain45 sites
  • Complejo Hospitalario de Albacete

    Albacete, 02006

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitari Vall Hebron

    Barcelona, 08035

  • Hospital Universitario de Basurto

    Bilbao, Vizcaya, 48013

  • Hospital Universitario de Burgos

    Burgos, 09006

  • Hospital San Pedro de Alcántara

    Cáceres, 10003

  • Hospital Puerta del Mar

    Cadiz

  • Hospital General Universitario Santa Lucía

    Cartagena, Murcia, 30200

  • Hospital General Univesitario de Castellón

    Castellon, Castellón, 12004

  • Complejo Hospitalario Regional Reina Sofía

    Córdoba, 14004

  • Hospital Universitario de Galdakao

    Galdakao, Vizcaya, 48960

  • Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • Hospital Juan Ramón Jiménez

    Huelva, 21005

  • Complejo Hospitalario de Jaén

    Jaén, 23007

  • Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria, Las Palmas, 35020

  • Complejo Hospitalario Lucus Augusti

    Lugo, 27003

  • Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Clínico San Carlos

    Madrid

  • Hospital La Paz

    Madrid

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Regional Universitario Málaga

    Málaga, 29010

  • Hospital Universitario Virgen de la Victoria

    Málaga, 29010

  • Hospital Virgen de la Arrixaca

    Murcia

  • Hospital Universitario Central de Asturias

    Oviedo, 33006

  • Complejo Universitario de Navarra

    Pamplona, 31008

  • Complejo Hospitalario de Pontevedra

    Pontevedra, 36071

  • Hospital Universitario Quirón Salud Madrid

    Pozuelo de Alarcón, Madrid, 28223

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital Universitario de Canarias

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

  • Hospital Universitario Marques de Valdecilla

    Santander, 39008

  • Complejo Hospitalario Universitario de A Coruña

    Santiago de Compostela, A Coruña, 15706

  • Complejo Hospitalario Universitario de Santiago

    Santiago de Compostela, A Coruña, 15706

  • Complejo Hospitalario Regional Virgen del Rocío

    Seville, 41013

  • Hospital Nuestra Señora del Prado

    Talavera de la Reina

  • Complejo Hospitalario de Toledo

    Toledo, 45004

  • Hospital Clínico Universitario Valencia

    Valencia, 46010

  • Hospital Universitario Dr. Peset Aleixandre

    Valencia, 46017

  • Hospital Universitari i Politecnic La Fe

    Valencia, 46026

  • Hospital Clínico Universitario de Valladolid

    Valladolid, 47003

  • Complejo Hospitalario Universitario de Vigo

    Vigo, Pontevedra, 36312

  • Hospital Txagorritxu

    Vitoria-Gasteiz, Álava, 01009

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, 50009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: A 2:1 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 AML

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

Read the detailed description

Multicenter, prospective, randomized, placebo-controlled, double-blinded phase II trial to assess the efficacy and safety of an oral quizartinib vs. placebo containing front-line chemotherapy-based schedule in FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) wild-type Acute Myeloid Leukemia patients.

The trial will be conducted in two phases:

An open-label safety run-in phase: Cytarabine 200 mg/m2 (days 1-7), Idarubicin 12 mg/m2 (days 1-3) Quizartinib 60 mg/d x 14 days (30mg with strong Cytochrome P450 Family 3 Subfamily A (CYP3A) inhibitor) in a total of 9 patients, being observed during 1 cycle of induction to define the final dose for the randomized phase.

A randomized double-blinded phase 2:1 quizartinib (at the established dose) vs. placebo.

Experimental Arm: Cytarabine 200 mg/m2 (days 1-7), Idarubicin 12 mg/m2 (days 1-3) Quizartinib 60 mg/d x 14 days (30mg with strong CYP3A inhibitor) Standard Arm: Cytarabine 200 mg/m2 (days 1-7), Idarubicin 12 mg/m2 (days 1-3) Placebo 60 mg/d x 14 days (30mg with strong CYP3A inhibitor)

272 patients will be included in this phase.

Being tested
Quizartinib, Placebo oral tablet, Cytarabine, Idarubicin
Keywords
Quizartinib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • QuizartinibDrug

    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.

  • Placebo oral tabletDrug

    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.

  • CytarabineDrug

    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.

  • IdarubicinDrug

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

Study groups in NCT04107727
Study groupRoleWhat they receive
QuizartinibExperimentalInduction: 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
Receives: Drug: Quizartinib; Drug: Cytarabine; Drug: Idarubicin
PlaceboPlacebo comparatorInduction: 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.
Receives: Drug: Placebo oral tablet; Drug: Cytarabine; Drug: Idarubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Through study completion, an average of 5 years

Secondary outcomes (6)
  1. Maximum dose tolerated (MDT) and recommended phase 2 dose (Safety run-in phase)

    To determine the maximum dose tolerated (MDT) and the recommended phase 2 dose

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

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

    The proportion of subjects with complete response or complete remission with incomplete blood count recovery with Minimal residual disease negative

    Measured: Through study completion, an average of 5 years

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

    Adverse events between experimental quizartinib containing schedule and standard arm

    Measured: Through study completion, an average of 5 years

  4. Disease-free survival

    To compare the time from the first documentation of remission to the documentation of disease recurrence or death.

    Measured: Through study completion, an average of 5 years

  5. Overall survival

    The number of days from randomization until death from any cause

    Measured: Through study completion, an average of 5 years

  6. Cumulative incidence of Relapse

    To compare the time from the date of first Complete Response until date of hematological or extramedullary relapse

    Measured: Through study completion, an average of 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2019
  2. Study start5 Sep 2019
  3. Primary completion3 Oct 2024
  4. Study completion24 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Safety run-in phase: multicenter, prospective, open-label. Phase II: multicenter, prospective, randomized, placebo-controlled, double-blinded
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
273 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04107727
Sponsor's protocol ID
QUIWI
Status last verified
Sep 2024
First submitted
25 Sep 2019
Last updated
24 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 41082703

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Quizartinib, Cytarabine and Idarubicin in people with Acute Myeloid Leukemia, run by PETHEMA Foundation at 45 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival rate (time frame: Through study completion, an average of 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04107727, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.

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