A Trial to Assess Cobicistat Boosted Venetoclax in Combination With Azacitidine in Adult Patients With Newly Diagnosed AML

Exclusion Criteria

• •A patient who meets any of the following criteria cannot be included in this study:
• •Acute promyelocytic leukemia.
• •Myelodysplastic syndrome (MDS).
• •Patients previously treated for AML or MDS (any anti-leukemic therapy including investigational agents; excluding: 1) erythropoiesis stimulating agents (ESAs); 2) hydroxyurea (hydroxyurea is allowed for the control of peripheral leukemic blasts in patients with leukocytosis).
• •Diagnosis of any previous or concomitant malignancy is an exclusion criterion:
• •* except when the patient successfully completed treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 24 months prior to registration;
• •* except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
• •Blast crisis of chronic myeloid leukemia.
• •Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.).
• •Cardiac dysfunction as defined by:
• •* Myocardial infarction within the last 3 months of study entry, or
• •* Reduced left ventricular function with an ejection fraction \< 40% as measured by MUGA scan or echocardiogram, or
• •* Unstable angina or New York Heart Association (NYHA) grade IV congestive heart failure (see Appendix G), or
• •* Unstable cardiac arrhythmias.
• •History of stroke or intracranial haemorrhage within 6 months prior to registration.
• •Symptomatic central nervous system (CNS) leukemia (NO routinely lumbar puncture required to investigate CNS involvement).
• •History of non-compliance to medical regimens or considered unreliable with respect to compliance.
• •Senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
• •Current concomitant chemotherapy, radiation therapy, or immunotherapy; other than hydroxyurea.
• •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
• •Unreplaceable use of strong inhibitors or inducers of CYP3A or CYP3A/p-GP substrates with a narrow therapeutic window (e.g. cobicistat or ritonavir for HIV treatment). Please check with Appendix I.
• •Intolerability, contra-indication or allergy to one of the study drugs.