Status:
RECRUITING
Venetoclax in Patients With MDS or AML in Relapse After AHSCT
Lead Sponsor:
Groupe Francophone des Myelodysplasies
Collaborating Sponsors:
AbbVie
Conditions:
MDS
AML
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
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 cel...
Detailed Description
A phase I-II study to assess venetoclax + azacitidine and donor lymphocyte infusion (DLI) in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in relapse after allohematopoi...
Eligibility Criteria
Inclusion
- 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
- Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an Follicle Stimulating Hormone (FSH) level \> 40 IU/L, or
- Permanent surgical sterility (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Female subjects of childbearing potential must have negative results for pregnancy test performed:
- At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
- Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been \> 7 days since obtaining the serum pregnancy test results.
- Female subjects who are not of childbearing potential at Screening do not require pregnancy testing.
- Male subjects sexually active with female partner(s) of childbearing potential, must agree from first dose of study drug(s) through at least 30 days after the last dose of venetoclax or 3 months after the last dose of azacitidine, whichever is later, to practice the protocol specified contraception.
- Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.
- Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.
- Patient is able to swallow capsules.
Exclusion
- 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 has received growth factors such as erythropoietin alfa (EPO) or granulocyte colony-stimulating factor (G-CSF) or has received non cytotoxic agents (including low dose oral chemotherapy) in the 30 days before inclusion. In case of previous cytotoxic treatment, an interval of 3 months is required.
- 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.
- Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration.
- Absence of social security.
Key Trial Info
Start Date :
November 23 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2027
Estimated Enrollment :
55 Patients enrolled
Trial Details
Trial ID
NCT05226455
Start Date
November 23 2022
End Date
December 1 2027
Last Update
October 3 2025
Active Locations (13)
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1
CHU d'Amiens Picardie - Site sud
Amiens, France, 80054
2
CHU d'Angers
Angers, France, 49933
3
CHU de Grenoble
Grenoble, France, 38043
4
Hôpital Dupuytren
Limoges, France, 87042