| Critètes d'exclusion |
- Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3 AML)
- Known active central nervous system (CNS) involvement with AML at study entry
- Prior exposure to Bcl-2 inhibitors, murine double minute 2 (MDM2) antagonists or prior exposure to experimental treatment targeting Raf, mitogen-activated protein kinase (MEK), or the mitogen-activated protein kinase (MAPK) RAS/RAF/MEK/ERK MAPK pathway
- Positive for hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and known history of HIV, malignancy, active infection and cardiovascular diseases (CVs)
- Received strong cytochrome (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers and moderate CYP3A inducers within 7 days prior to initiation of study treatment
- History of symptomatic Clostridium difficile infection within 1 month prior to dosing
- Additional phase specific exclusion criteria:
- Phase Ib Dose Escalation Arm A (Venetoclax and Cobimetinib)
- History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower
- Phase Ib Dose-Escalation Arm B (Venetoclax and Idasanutlin):
- Received the following within 7 days prior to the initiation of study treatment:
- Strong CYP2C8 inhibitors or CYP2C8 substrates
- OATP1B1/3 substrates
- Received the following within 14 days prior to the initiation of study treatment:
- * Strong CYP2C8 inducers
- Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
- History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
- Phase II Expansion Arm A and Arm B:
-
Received the following within 7 days prior to the initiation of study treatment:
- Strong CYP2C8 inhibitors or CYP2C8 substrates
- OATP1B1/3 substrates
-
Received the following within 14 days prior to the initiation of study treatment:
* Strong CYP2C8 inducers
- History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/CSCR, RVO, or neovascular macular degeneration
- LVEF below institutional LLN or below 50%, whichever is lower
- Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
- History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
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HOPITAL GENERAL JUIF SIR MORTIMER B.DAVIS
Groupe d'étude en oncologie du Québec