Study of the safety and efficacy of treatment venetoclax + azacitidine and donor lymphocyte infusion in patients with MDS or AML in relapse after transplantation

Prior treatment

• 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
• Subject has received strong or moderate CYP3A 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 currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug

Other illness

• Patient has active and uncontrolled infection
• Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs
• Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration
• 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 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 AZA

Age

• 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

Other

• Patients with clinical evidence of CNS leukemia
• Patient is pregnant or breastfeeding within the projected duration of the study
• Absence of social security
• Patient has active acute or chronic GVHD
• Patient receives more than 1mg/kg/day prednisolone

• Documented relapse of MDS or AML (with WBC < 15000/mm3) after allo-SCT
• Patient is able to swallow capsules
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• 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)
• 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
• 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