NCT06668558

Venetoclax + Azacitidine in Patients With Acute Myeloid Leukemia

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)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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%).

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
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)

Timeline

• Start date: 2024-12-16
• Primary completion: 2028-06-01
• Completion: 2028-07-01
• First posted: 2024-10-31
• Last updated: 2025-09-19

Locations

14 sites across 1 country: Spain