NCT07478991

Brief Summary

The goal of this clinical trial is to learn if Venetoclax+Azacytidine+Quizartinib works better than standard therapy (Venetoclax+Azacytdine) to treat naïve adult patients with acute myeloid leukemia (AML) who are not suitable for standard induction therapy due to age, co-morbidities or other risk factors. The main question it aims to answer is: \- Does the combination of Venetoclax+Azacytidine+Quizartinib show more probability of overall survival than Venetoclax+Azacytdine? Researchers will compare Venetoclax+Azacytidine+Quizartinib to Venetoclax+Azacytdine to see if Venetoclax+Azacytidine+Quizartinib works better than Venetoclax+Azacytdine to treat AML. Participants will be randomized to one of the two treatment arms in a 1:1 ratio, both of which will have treatment cycles of 28 days.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
376

participants targeted

Target at P50-P75 for phase_3

Timeline
45mo left

Started Jul 2026

Typical duration for phase_3

Geographic Reach
1 country

51 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress3%
Jul 2026Apr 2030

First Submitted

Initial submission to the registry

March 13, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 18, 2026

Completed
4 months until next milestone

Study Start

First participant enrolled

July 2, 2026

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2030

Last Updated

August 3, 2026

Status Verified

March 1, 2026

Enrollment Period

3.8 years

First QC Date

March 13, 2026

Last Update Submit

July 31, 2026

Conditions

Keywords

AMLadultold/unfit

Outcome Measures

Primary Outcomes (1)

  • Overall Survival

    Comparison of time from diagnosis to death or last follow-up between both treatment arms.

    4 years

Secondary Outcomes (2)

  • Event-free Survival rate

    4 years

  • Composite Complete Response (CCR) rate

    4 years

Study Arms (2)

Venetoclax Azacitidine and Quizartinib

EXPERIMENTAL

* Azacytidine 75 mg/m2 /daily SC, days 1 to 7 in 28-day cycle. * Venetoclax 400 mg/daily oral for days 1 to 7, the same days as Azacytidine, in 28-day-cycle. * Quizartinib 60 mg/daily oral in FLT3-ITD negative and 40 mg daily in FLT3-ITD positive patients, days 8 to 21.

Drug: AzacitidineDrug: VenetoclaxDrug: Quizartinib

Venetoclax and Azacitidine

ACTIVE COMPARATOR

* Azacytidine 75 mg/m2 /daily SC, days 1 to 7 in 28-day cycle. * Venetoclax 400 mg/daily oral for days 1 to 7, the same days as Azacytidine, in 28-day-cycle.

Drug: AzacitidineDrug: Venetoclax

Interventions

Subcutaneous injection during the first 7 days of each 28-day cycle until disease progression or end of study

Venetoclax Azacitidine and QuizartinibVenetoclax and Azacitidine

Oral Venetoclax during the first 7 days of each 28-day cycle until disease progression or end of study

Venetoclax Azacitidine and QuizartinibVenetoclax and Azacitidine

Oral Quizartinib during days 8 to 21 of each 28-day cycle until disease progression or end of study .

Venetoclax Azacitidine and Quizartinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • The subject must have confirmation of AML by 2022 WHO criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline based induction regimen due to age and/or comorbidities.
  • Patients must be considered ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or co-morbidities defined by the following criteria:
  • ≥ 75 years of age;
  • or ≥ 18 to 75 years of age with at least one of the following co-morbidities:
  • ECOG Performance Status of 2 or 3;
  • Cardiac history of cardiac heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) \>45% and ≤ 55% or chronic stable angina.
  • DLCO ≤ 65% or FEV1 ≤ 65% and/or significant history of chronic pulmonary obstructive;
  • Creatinine clearance ≥ 30 mL/min to \< 50 ml/min (see Appendix 7);
  • Moderate hepatic impairment with total bilirubin, SGPT or SGOT \> 1.5 to ≤ 3.0 × ULN;
  • Non active/controlled prior neoplastic disease;
  • Any other patient´s comorbidity or disease condition that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Clinical Trial Coordinator before study enrollment (e.g, prior neoplastic disease, high-risk cytogenetics). All patients aged less than 60 years old must be reviewed and approved by Clinical Trial Coordinator before study enrollment.
  • ECOG performance status ≤2 for patients \>75 years, ≤3 for patients ≥ 60 to 75 years of age.
  • Male subjects who are sexually active, must agree, from Study Day 1 through at least 120 days after the last dose of study drug, to practice the protocol specified contraception.
  • Female subjects must be either postmenopausal for at least 1 year before screening OR permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy) or Women of Childbearing Potential (WOCBP) must agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 7 months after the last dose of study drug (female and male condoms should not be used together), or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception). Female subjects of childbearing potential must have negative results for pregnancy test performed and must not be lactating and breastfeeding.
  • Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

You may not qualify if:

  • Age \<18 years old at screening.
  • Subject has received prior treatment with hypomethylating agent, FLT3 or BCL2 inhibitors.
  • Genetic diagnosis of acute promyelocytic leukemia.
  • Treated (excluding surgery or hormone-therapy) for another malignancy within 6 months before randomization or previously diagnosed with another malignancy and have any evidence of disease which may compromise the administration of investigational treatment schedule.
  • Serum creatinine ≥ 2.5 mg/dL or creatinine clearance \< 30 mL/min.
  • Bilirubin \>1.5 times, SGPT or SGOT \> 3 times the upper normal limit (unless it is attributable to AML activity).
  • WBC \>25 x 109/L before randomization.
  • Contraindications for Azacitidine, Quizartinib or Venetoclax (such as history of hypersensitivity to any excipients in Azacitidine, Quizartinib, or Venetoclax).
  • Known central nervous system (CNS) active leukemia, including cerebrospinal fluid positive for AML blasts.
  • Prior treatment with any investigational drug or device within 14 days prior to Randomization (within 2 weeks for investigational or approved immunotherapy) or currently participating in other investigational interventional procedures.
  • Known uncontrolled or significant cardiovascular disease, including any of the following:
  • Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;
  • QTcF interval \>450 msec;
  • 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;
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (51)

Complejo Hospitalario Universitario de A Coruña

Santiago de Compostela, A Coruña, 15706, Spain

NOT YET RECRUITING

ICO Hospitalet- Hospital Duran i Reynals

Hospitalet Del Llobregat, Barcelona, 08908, Spain

RECRUITING

Hospital Mútua de Terrassa

Terrassa, Barcelona, Spain

RECRUITING

Complejo Hospitalario de Jaén

Jaén, Jaen, 23007, Spain

RECRUITING

Hospital Principe de Asturias

Alcalá de Henares, Madrid, Spain

NOT YET RECRUITING

Hospital Universitario Infanta Sofía

San Sebastián de los Reyes, Madrid, 28702, Spain

NOT YET RECRUITING

Hospital Regional Universitario de Málaga

Málaga, Malaga, 29010, Spain

NOT YET RECRUITING

Hospital Universitario de Cruces

Barakaldo, Vizcaya, 48903, Spain

NOT YET RECRUITING

Complejo Hospitalario de Albacete

Albacete, 02006, Spain

NOT YET RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, Spain

NOT YET RECRUITING

Hospital Universitario Torrecárdenas

Almería, Spain

NOT YET RECRUITING

Institut Catalá d´Oncología (ICO Badalona)

Badalona, Spain

NOT YET RECRUITING

Hospital Galdakao-Usansolo

Barakaldo, Spain

RECRUITING

Hospital Universitario de Basurto

Barakaldo, Spain

NOT YET RECRUITING

Hospital Universitario de Burgos

Burgos, Spain

NOT YET RECRUITING

Hospital Universitario Puerta del Mar

Cadiz, Spain

NOT YET RECRUITING

H. General de Castellón

Castelló, Spain

NOT YET RECRUITING

Complejo Hospitalario de Cáceres

Cáceres, Spain

NOT YET RECRUITING

Complejo Hospitalario Regional Reina Sofía

Córdoba, 14004, Spain

NOT YET RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, Spain

NOT YET RECRUITING

Hospital Universitario Juan Ramón Jiménez

Huelva, 21005, Spain

NOT YET RECRUITING

Complejo Hospitalario de Gran Canaria Dr. Negrin

Las Palmas de Gran Canaria, Spain

RECRUITING

Complejo Hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, Spain

NOT YET RECRUITING

Hospital Universitario de Canarias

Las Palmas de Gran Canaria, Spain

RECRUITING

Hospital Universitario Lucus Augusti

Lugo, Spain

NOT YET RECRUITING

Fundación Jiménez Díaz

Madrid, Spain

NOT YET RECRUITING

HLA Hospital Universitario Moncloa

Madrid, Spain

NOT YET RECRUITING

Hospital Clínico San Carlos

Madrid, Spain

NOT YET RECRUITING

Hospital Infanta Leonor

Madrid, Spain

NOT YET RECRUITING

Hospital Univeristario Ramón y Cajal

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, Spain

NOT YET RECRUITING

HU Quirónsalud Madrid

Madrid, Spain

NOT YET RECRUITING

H.U. Puerta de Hierro Majadahonda

Majadahonda, Spain

NOT YET RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, Spain

RECRUITING

Hospital Clinico Universitario Virgen de La Arrixaca

Murcia, Spain

RECRUITING

Clínica Universitaria de Navarra

Pamplona, Spain

NOT YET RECRUITING

Hospital Virgen Del Puerto

Plasencia, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Salamanca.

Salamanca, Spain

NOT YET RECRUITING

Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, 38010, Spain

NOT YET RECRUITING

H. Marqués de Valdecilla

Santander, Spain

NOT YET RECRUITING

Hospital de Santiago de Compostela

Santiago de Compostela, Spain

NOT YET RECRUITING

Hospital General de Segovia

Segovia, Spain

NOT YET RECRUITING

Hospital Universitario Virgen de Valme

Seville, Spain

NOT YET RECRUITING

Hospital Universitario Virgen Del Rocío

Seville, Spain

NOT YET RECRUITING

Hospital General Universitario de Toledo

Toledo, Spain

NOT YET RECRUITING

H. Dr. Peset

Valencia, Spain

NOT YET RECRUITING

Hospital Arnau de Vilanova-Valencia

Valencia, Spain

RECRUITING

Hospital General de Valencia

Valencia, Spain

RECRUITING

Hospital Universitari i Politècnic La Fe

Valencia, Spain

NOT YET RECRUITING

H. Río Hortega

Valladolid, Spain

RECRUITING

Hospital Álvaro Cunqueiro

Vigo, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidinevenetoclaxquizartinib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Officials

  • Claudia Sossa

    Clínica FOSCAL

    PRINCIPAL INVESTIGATOR
  • Joana Brioso

    Centro Hospitalar Universitário Lisboa Norte Hospital de Santa Maria

    PRINCIPAL INVESTIGATOR
  • Juan Bergua

    Hospital San Pedro Alcántara

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan José Lahuerta

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 13, 2026

First Posted

March 18, 2026

Study Start

July 2, 2026

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

April 1, 2030

Last Updated

August 3, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations