Venetoclax + Azacitidine in Patients With Acute Myeloid Leukemia (VERDI)

September 15, 2025 updated by: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Preemptive Treatment With Venetoclax Plus Azacitidine in Patients Diagnosed With Acute Myeloid Leukemia (AML) With Persistence or Reappearance of Measurable Residual Disease (MRD) After Frontline Chemotherapy and High-level MRD Prior to Allogeneic Hematopoietic Cell Transplantation (alloHCT)

The VERDI study is an investigator-initiated, multicenter, multicohort, phase II trial with combination of venetoclax + azacitidine for patients treated for AML under according to an intensive chemotherapy protocol (CETLAM-20) failing to achieve or maintain MRD negativity at pre-established time-points: at chemotherapy completion for ELN favorable subtypes, and prior to alloHCT for non-favorable European LeukemiaNet (ELN) AML patients.

The primary objective is to determine Ven/Aza treatment activity in MRD clearance in patients diagnosed with AML with persistent MRD or MRD reappearance after frontline chemotherapy, or prior to alloHCT.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The trial will enroll competitively between 25 and 29 patients.

Patients will be recruited in two independent cohorts depending on the pre-established time point for the intervention and ELN risk subtype:

Cohort 1: Patients diagnosed with a favorable ELN subtype AML, not intended for alloHCT in first complete remission (CR1), but who present an MRD failure by after frontline intensive chemotherapy, as defined in the 2021 update on MRD guidelines elaborated by the European LeukemiaNet MRD Working Party (Heuser et al. 2023):

In patients with persistent low-level MRD (<2%) after consolidation chemotherapy, an increase of MRD ≥1log10 between 2 positive samples Confirmed MRD conversion of MRD negativity to MRD positivity AML during subsequent follow-up (up to 3 years after chemotherapy completion

Cohort 2: Patients diagnosed with a non-favorable ELN AML subtype, intended to undergo alloHCT, in first complete morphological remission but harboring detectable MRD at time of alloHCT (>0.1%).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: A Responsible Person Designated by the sponsor
  • Phone Number: 0034934344412
  • Email: investigacio@mfar.net

Study Locations

  • Spain
    • Balearic Islands
      • Palma de Mallorca, Balearic Islands, Spain, 07198
        • Recruiting
        • Hospital Son Llatzer
        • Contact:
        • Principal Investigator:
          • Antonia Cladera, M.D.; Ph.D.
      • Palma de Mallorca, Balearic Islands, Spain, 07120
        • Recruiting
        • University Hospital Son Espases
        • Contact:
        • Principal Investigator:
          • Antonia Sampol, M.D.; Ph.D.
    • Catalonia
      • Badalona, Catalonia, Spain, 08916
        • Recruiting
        • Institut Catala d Oncologia Badalona
        • Contact:
        • Principal Investigator:
          • Susana Vives, M.D.; Ph.D.
      • Barcelona, Catalonia, Spain, 08025
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
        • Principal Investigator:
          • Ana Garrido, M.D.; Ph.D.
      • Barcelona, Catalonia, Spain, 08036
        • Recruiting
        • Hospital Clinic de Barcelona
        • Contact:
        • Principal Investigator:
          • Jordi Esteve, M.D.; Ph.D.
      • Barcelona, Catalonia, Spain, 08003
        • Recruiting
        • Hospital del Mar
        • Contact:
        • Principal Investigator:
          • Sara García, M.D.; Ph.D.
      • Barcelona, Catalonia, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall D Hebron
        • Contact:
        • Principal Investigator:
          • Olga Salamero, M.D.; Ph.D.
      • Girona, Catalonia, Spain, 17007
        • Recruiting
        • Institut Catala D oncologia Girona
        • Contact:
        • Principal Investigator:
          • Rosa Coll Jorda, M.D.; Ph.D.
      • L'Hospitalet de Llobregat, Catalonia, Spain, 08908
        • Recruiting
        • Institut Catala d Oncologia Hospitalet
        • Contact:
        • Principal Investigator:
          • Montserrat Arnan, M.D.; Ph.D.
      • Lleida, Catalonia, Spain, 25196
        • Recruiting
        • Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida
        • Contact:
        • Principal Investigator:
          • Antonio García, M.D.; Ph.D.
      • Tarragona, Catalonia, Spain, 43005
        • Recruiting
        • Hospital Universitari Joan XXIII de Tarragona
        • Contact:
        • Principal Investigator:
          • Luiz Andre Aguilar, M.D.; Ph.D.
      • Terrassa, Catalonia, Spain, 08221
        • Recruiting
        • Fundacio Assistencial De Mutua De Terrassa
        • Contact:
        • Principal Investigator:
          • Ferran Vall-Llovera, M.D.; Ph.D.
    • Madrid
      • Madrid, Madrid, Spain, 28009
        • Recruiting
        • Hospital General Universitario Gregorio Marañón
        • Contact:
        • Principal Investigator:
          • Mi Kwon, M.D.; Ph.D.
    • Valencia
      • Valencia, Valencia, Spain, 46010
        • Recruiting
        • Hospital Clínico Universitario de Valencia
        • Contact:
        • Principal Investigator:
          • Mar Tormo, M.D.; Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients must have confirmation of with acute myeloid leukemia (AML) with persistent measurable residual disease (MRD) or MRD reappearance after frontline intensive chemotherapy (including at least one cycle of cytarabine and anthracycline), and prior to allogeneic hematopoietic cell transplantation (allo-HCT).

    1. In patients with NPM1 mutation, qRT-PCR of NPM1 will be the method used to establish a molecular failure, defined as failure to achieve molecular response after consolidation therapy (NPM1mut/ABL1·100 > 0.1) or MRD reappearance after molecular response. All cases of molecular failure must be confirmed with a second MRD assessment in 2 to 4 weeks.
    2. In patients with core-binding factor AML, qRT-BCR of RUNX1-RUNX1T1 and CBFb-MYH11 transcripts will be used. Patients failing to achieve a major MRD reduction after consolidation therapy (i.e., RUNX1-RUNX1T1/ABL1·100>0.1 or CBFb-MYH11/ABL1·100>0.1), a log increase in MRD between two positive samples or confirmed MRD reappearance after molecular response will be considered as molecular failures and could be included in the trial.
    3. In the remaining cases, an appropriate leukemia-associated immunophenotype (LAIP) measured by multiparameter flow cytometry will be used for MRD surveillance. A cutoff of 0.1% will be used to define MRD positivity.
  2. Age ≥18 years.
  3. Without clinical signs of active central nervous system disease.
  4. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2 or Karnofsky performance status (KPS) equivalent.
  5. Patients must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.

  6. Patients must have adequate liver function as demonstrated by:

    1. aspartate aminotransferase (AST) ≤ 3.0 × upper limit normal (ULN)
    2. alanine aminotransferase (ALT) ≤ 3.0 × ULN
    3. bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome
  7. Non-sterile male patients must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 3 months after the last dose of study drug. Male patients must agree to refrain from sperm donation from initial study drug administration until 3 months after the last dose of study drug.
  8. WOCBP must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting therapy; 2) throughout the entire duration of treatment; 3) during dose interruptions; and 4) for at least 6 months after discontinuation of therapy (last dose of study drug).
  9. Patients must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed screening procedures.

Exclusion Criteria:

  1. Patient has received other prior rescue treatment for MRD.

  2. Patient is known to be positive for Human immunodeficiency virus (HIV) infection with the exception of those with an undetectable viral load under correct virological control throughout the study.

    Note: HIV testing is not required.

  3. Patient is known to be positive for hepatitis B (HBV) or C (HCV) infection with the exception of those with an undetectable viral load.

    Note: Hepatitis B or C testing is not required and patients with serologic evidence of prior vaccination to HBV (i.e., HBsAg-, anti-HBs+ and anti-HBc-) may participate.

  4. Patient has known active central nervous system (CNS) involvement from AML.
  5. Patient has received within 7 days prior to the first dose of study drug: steroid therapy ≥ 20 mg/day (prednisone or equivalent) for antineoplastic intent; strong and moderate CYP3A inhibitors; strong and moderate CYP3A inducers.
  6. Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.

  7. Patient has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:

    1. New York Heart Association heart failure > class 2.
    2. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
  8. Patient has a malabsorption syndrome or other condition that precludes the enteral route of administration.
  9. Patient exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

  10. Patient has a history of other malignancies within the prior year to study entry, except for:

    1. Adequately treated in situ carcinoma of the breast or cervix uteri.
    2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.
    3. Prostate cancer with no plans for therapy of any kind.
    4. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  11. Pregnant and breastfeeding females.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1
Patients diagnosed with a favorable ELN subtype AML, not intended for alloHCT in CR1, but who present an MRD failure by after frontline intensive chemotherapy, as defined in the 2021 update on MRD guidelines elaborated by the European LeukemiaNet MRD Working Party (Heuser et al. 2021)
Drug: Azacitidine (AZA)

Dosing is 75 mg/m2 x 7 days (Q28days) After 2 courses, a first decision-making for allo-HCT based on bone marrow MRD assessment will be performed. After 4th course, a new MRD assessment will be performed.

For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)

Drug: Venetoclax

Dosing: 400 mg daily After 2 courses, a first decision-making for allo-HCT based on bone marrow MRD assessment will be performed. After 4th course, a new MRD assessment will be performed.

For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)
Experimental: Cohort 2
Patients diagnosed with a non-favorable ELN AML subtype, intended to undergo alloHCT, in first complete morphological remission but harboring detectable MRD at time of alloHCT (>0.1%)
Drug: Azacitidine (AZA)

Dosing is 75 mg/m2 x 7 days (Q28days) After 2 courses, a first decision-making for allo-HCT based on bone marrow MRD assessment will be performed. After 4th course, a new MRD assessment will be performed.

For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)

Drug: Venetoclax

Dosing: 400 mg daily After 2 courses, a first decision-making for allo-HCT based on bone marrow MRD assessment will be performed. After 4th course, a new MRD assessment will be performed.

For cohort 1 treatment may continue up to cycle 12 (prioritized over allo-HCT). For cohort 2 treatment may continue up to cycle 24 (prioritizing allo-HCT)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Rate of MRD conversion after 2 to 4 courses of study treatment
Time Frame: After the administration of 2 and 4 cycles (i.e. approximately 2 and 4 months after. Throughout the study period (up to 3 years) the initiation of study treatment)
Defined as the percentage of patients who achieve MRD clearance after 2-4 courses of study treatment. Failure to achieve MRD negativity after 4 courses will be considered a treatment failure.
After the administration of 2 and 4 cycles (i.e. approximately 2 and 4 months after. Throughout the study period (up to 3 years) the initiation of study treatment)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of MRD response
Time Frame: Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Defined as the time elapsed from the first obtention of MRD clearance until MRD progression. Confirmed MRD conversion from MRD negativity to MRD positivity will be performed during subsequent follow-up.
Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Relapse risk after intervention
Time Frame: Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Defined as the time elapsed from the intervention for AML until confirmed hematological relapse.
Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Safety profile
Time Frame: Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Incidence of Treatment-Emergent Adverse Events Percentage of patients experiencing treatment-related adverse events (AEs).
Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Treatment Compliance
Time Frame: Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)
Percentage of patients experiencing AEs that lead to dose modifications, including treatment interruption, delays and dose reductions.
Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jordi Esteve, M.D.; Ph.D., Hematology department Institute Clínic of Hematological and Oncological diseases (ICMHO) Hospital Clínic of Barcelona

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 16, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 31, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CETLAM-LMA-AC-2024-01
  • 2024-510648-29-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

To protect confidentiality of patients the IPD will be restricted and only shared upon reasonable request if the purposes of this request complies with the conditions agreed with patients consent.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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