VENETOCLAX for Myelodysplastic syndromes | Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Documented relapse of MDS or AML (with WBC < 15000/mm3) after allo-SCT"}
• {"criterion_text":"- Patient is able to swallow capsules"}
• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2"}
• {"criterion_text":"- Patient must have adequate organ function as indicated by the following laboratory values: Serum creatinine < 2 mg/dl OR calculated creatinine clearance ≥ 30 mL/min for patients with creatinine levels > 1.5 x institutional ULN ; Serum total bilirubin ≤ 2.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels ≥ 2 mg/dL ; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN ; Alkaline Phosphatase ≤ 5 x ULN (If > 2.5 x ULN, then liver fraction should be ≤ 2.5 x ULN)"}
• {"criterion_text":"- Patient not refractory to platelet transfusions"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study"}
• {"criterion_text":"- Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study"}

Exclusion criteria

• {"criterion_text":"- Patient has active and uncontrolled infection"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Patients with clinical evidence of CNS leukemia"}
• {"criterion_text":"- Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs"}
• {"criterion_text":"- Subject has received strong or moderate CYP3A inhibitors within 3 days prior to the first dose of study drug"}
• {"criterion_text":"- Patient is unable to take and/or tolerate oral medications on a continuous basis"}
• {"criterion_text":"- Patient is pregnant or breastfeeding within the projected duration of the study"}
• {"criterion_text":"- Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration"}
• {"criterion_text":"- Absence of social security"}
• {"criterion_text":"- Patient has active acute or chronic GVHD"}
• {"criterion_text":"- Patient receives more than 1mg/kg/day prednisolone"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy"}
• {"criterion_text":"- Patient has clinically active hepatitis B or hepatitis C infection"}
• {"criterion_text":"- Patient has a known allergy or hypersensitivity to any component of VENETOCLAX or AZA"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Phase I: To determine toxicity profile and safety of the combination","definition_or_measurement_approach":""}
• {"endpoint_text":"- Phase II: Overall hematological response rate of venetoclax in combination with AZA/DLI. Response assessment will be performed for MDS according to IWG criteria and according to European LeukemiaNet criteria for AML.","definition_or_measurement_approach":"Response assessment: for MDS according to IWG criteria; for AML according to European LeukemiaNet (ELN) criteria."}

Secondary endpoints

• {"endpoint_text":"- Toxicity as measured by NCI CTCAE 5.0","definition_or_measurement_approach":"Measured by NCI CTCAE version 5.0"}
• {"endpoint_text":"- Acute and chronic GVHD rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Event-free survival","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

19-08-2024

Latest Decision Or Authorization Date

16-04-2025

Processing Time Days

240

Number Of Sites

16

Number Of Participants

55

Primary sponsor

Full Name

Groupe Francophone Des Myelodysplasies

Organisation Type

Patient organisation/association

Country Of Registered Address

France