Venetoclax in Patients With MDS or AML in Relapse After AHSCT

NCT05226455 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: VENTOGRAFT2024-514877-23-00
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 11

Brief Summary

Study to assess venetoclax + azacitidine and donor lymphocyte infusion (DLI) in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in relapse after allohematopoietic stem cell transplantation (AHSCT).

Conditions

MDS; AML

Keywords

MDS; AML; AHSCT; Venetoclax; Azacitidine; DLI

Outcome Measures

Primary Outcomes (2)

• Phase I: Dose-finding study

  Evaluation of Dose-limiting toxicity (DLT) to determine the optimal dose level in terms of both toxicity and safety for venetoclax + azacitidine

  At the end of cycle 1 of venetoclax + azacitidine (each cycle is 28 days)

• Phase II: Overall improvement rate of venetoclax + azacitidine +/- DLI

  Response assessment performed according to modified IWG (International Working Group) 2006 criteria for myelodysplastic syndrome and to European Leukemia Net criteria for acute myeloid leukemia

  After 8 cycles of venetoclax + azacitidine (each cycle is 28 days)

Secondary Outcomes (6)

• Toxicity assessment

  At 60 months (at end of study)

• Graft-versus-Host-Disease (GVHD) rate

  At 60 months (at end of study)

• Duration of response

  At 60 months (at end of study)

• Overall survival

  At 60 months (at end of study)

• Progression-free survival

  At 60 months (at end of study)

Other Outcomes (2)

• Correlation between patient overall mutational status before and after treatment

  At 60 months (at end of study)

• Prognostic impact of Minimal Residual Disease (MRD) on outcome

  At 60 months (at end of study)

Study Arms (1)

venetoclax + azacitidine +/- donor lymphocyte infusion

EXPERIMENTAL

Venetoclax + azacitidine +/- donor lymphocyte infusion (maximum 12 cycles). Venetoclax: on D1 to D14 of 28 days cycle ; Phase I: 4 dose levels: 50, 100, 200, 400 mg/d, starting dose at 100 mg ; Phase II: dose defined in the phase I. Azacitidine 75 mg/m²/d or 50 mg/m²/d (if allohematopoietic stem cell transplantation relapse \< 4 months) x 5 days (on D1 to D5 of 28 days cycle).

Drug: venetoclax + azacitidine +/- donor lymphocyte infusion

Interventions

venetoclax + azacitidine +/- donor lymphocyte infusion DRUG

Venetoclax will be given once daily orally on days 1 to 14 for all cycles. Venetoclax + azacitidine +/- donor lymphocyte infusion (12 cycles maximum)

Also known as: venclyxto, vidaza

venetoclax + azacitidine +/- donor lymphocyte infusion

Eligibility Criteria

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

You may qualify if:

• Documented cytologic relapse of MDS according to FAB/WHO classification 2016 (including CMML with WBC \< 13000/mm3) or AML, with WBC \< 15000/mm3, after allo-SCT.
• Relapse of MDS or AML is defined as :
• Return to pretreatment bone marrow blast percentage
• Decrement of at least 50% from maximum remission
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must have adequate organ function:
• Serum creatinine \< 2 mg/dL or calculated creatinine clearance ≥ 30 mL/min for patients with creatinine levels \> 1.5 times Upper Limit of Normal
• Serum total bilirubin ≤ 2.5 times Upper Limit of Normal or direct bilirubin ≤ Upper Limit of Normal for patients with total bilirubin levels ≥ 2 mg/d
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times Upper Limit of Normal
• Alkaline phosphatase ≤ 5 times Upper Limit of Normal (if \> 2.5 times Upper Limit of Normal, then liver fraction should be ≤ 2.5 times Upper Limit of Normal).
• Patient not refractory to platelet transfusions.
• Female subject of childbearing potential must practice at least one protocol specified method of birth control, starting on Study Day 1 through at least 30 days after the last dose of venetoclax or 6 months after the last dose of azacitidine.
• Not being of childbearing potential is defined as:
• Age \> 55 years with no menses for 12 or more months without an alternative medical cause, or

You may not qualify if:

• Patient has active and uncontrolled infection.
• Patient has active acute or chronic Graft-versus-Host-Disease (GVHD).
• Patient receives more than 1mg/kg/day prednisolone.
• Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug.
• Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
• Patient has clinically active hepatitis B or hepatitis C infection.
• Patient has a known allergy or hypersensitivity to any component of venetoclax or azacitidine.
• Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \> 2 years or are considered by their physician to be at less than 30% risk of relapse.
• Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs.
• Patients with clinical evidence of Central Nervous System leukemia.
• Patient has a history of Gastrointestinal surgery or other procedures that might interfere with the absorption or swallowing of the study drugs.
• Subject has received strong or moderate CYP3A (Cytochrome P450, family 3, subfamily A) inhibitors within 3 days prior to the first dose of study drug.
• Patient is unable to take and/or tolerate oral medications on a continuous basis.
• Patient is pregnant or breastfeeding within the projected duration of the study.

Sponsors & Collaborators

• AbbVie: collaborator
• Groupe Francophone des Myelodysplasies: lead

Study Sites (11)

CHU d'Angers

Angers, 49933, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Hôpital Dupuytren

Limoges, 87042, France

Location

Hôpital Saint-Eloi

Montpellier, 34295, France

Location

CHU Hôtel Dieu

Nantes, 44093, France

Location

Hôpital l'Archet I

Nice, 06200, France

Location

Hôpital Saint louis

Paris, 75010, France

Location

CHU de Haut-Lévèque

Pessac, 33604, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

IUCT Oncopole

Toulouse, 31059, France

Location

MeSH Terms

Interventions

venetoclax; Azacitidine

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

• Thomas CLUZEAU, PHD

  CHU de Nice - Hôpital l'Archet I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 7, 2022
• Study Start: November 23, 2022
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

FR (11)