Venetoclax + Azacitidine in Patients With Acute Myeloid Leukemia

NCT06668558 | Recruiting Phase 2

• 2 other identifiers: CETLAM-LMA-AC-2024-012024-510648-29-00
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Keywords

venetoclax; azacitidine; measurable residual disease (MRD); allogeneic hematopoietic cell transplantation (alloHCT)

Outcome Measures

Primary Outcomes (1)

• Rate of MRD conversion after 2 to 4 courses 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 Outcomes (4)

• Duration of MRD response

  Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)

• Relapse risk after intervention

  Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)

• Safety profile

  Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)

• Treatment Compliance

  Throughout the study period, up to 3 years after chemotherapy completion. Throughout the study period (up to 3 years)

Study Arms (2)

Cohort 1

EXPERIMENTAL

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); Drug: Venetoclax

Cohort 2

EXPERIMENTAL

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); Drug: Venetoclax

Interventions

Azacitidine (AZA) DRUG

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)

Cohort 1; Cohort 2

Venetoclax DRUG

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)

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.
• 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.
• 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.
• Age ≥18 years.
• Without clinical signs of active central nervous system disease.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤2 or Karnofsky performance status (KPS) equivalent.
• 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.
• Patients must have adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 3.0 × upper limit normal (ULN)
• alanine aminotransferase (ALT) ≤ 3.0 × ULN
• bilirubin ≤ 1.5 × ULN, unless due to Gilbert\'s syndrome
• 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.
• 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).
• 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.

You may not qualify if:

• Patient has received other prior rescue treatment for MRD.
• 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.
• 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.
• Patient has known active central nervous system (CNS) involvement from AML.
• 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.
• 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.
• 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:
• New York Heart Association heart failure \> class 2.
• Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
• Patient has a malabsorption syndrome or other condition that precludes the enteral route of administration.
• Patient exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
• Patient has a history of other malignancies within the prior year to study entry, except for:
• Adequately treated in situ carcinoma of the breast or cervix uteri.

Sponsors & Collaborators

• Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias: lead

Study Sites (14)

University Hospital Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

RECRUITING

Hospital Son Llatzer

Palma de Mallorca, Balearic Islands, 07198, Spain

RECRUITING

Institut Catala D oncologia Badalona

Badalona, Catalonia, 08916, Spain

RECRUITING

Hospital Del Mar

Barcelona, Catalonia, 08003, Spain

RECRUITING

Hospital De La Santa Creu I Sant Pau

Barcelona, Catalonia, 08025, Spain

RECRUITING

Hospital Universitari Vall D Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Clinic De Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Institut Catala D oncologia Girona

Girona, Catalonia, 17007, Spain

RECRUITING

Institut Catala D oncologia Hospitalet

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

RECRUITING

Hospital Universitari Arnau De Vilanova De La Gerencia Territorial De Lleida

Lleida, Catalonia, 25196, Spain

RECRUITING

Hospital Universitari Joan XXIII De Tarragona

Tarragona, Catalonia, 43005, Spain

RECRUITING

Fundacio Assistencial De Mutua De Terrassa

Terrassa, Catalonia, 08221, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, Madrid, 28009, Spain

RECRUITING

Hospital Clinico Universitario De Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Neoplasm, Residual

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jordi Esteve, M.D.; Ph.D.

  Hematology department Institute Clínic of Hematological and Oncological diseases (ICMHO) Hospital Clínic of Barcelona

  STUDY CHAIR

Central Study Contacts

A responsible person Designated by the sponsor

CONTACT

0034934344412; investigacio@mfar.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: investigator-initiated, multicenter, multicohort, phase II trial

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: October 31, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

ES (14)