A Study of Venetoclax in Combination With Cobimetinib and Venetoclax in Combination With Idasanutlin in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Are Not Eligible for Cytotoxic Therapy

Completed · Phase 1

Conditions studied: Leukemia, Myeloid, Acute

In brief

The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients with relapsed or refractory acute myeloid leukemia (R/R) AML who are not eligible for cytotoxic therapy.

Key facts

Study ID

NCT02670044

Run by

Hoffmann-La Roche

People needed

88

Starts

2016-03-09

Expected to finish

2020-12-10

Last updated by the study team

2022-01-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO classification
• Ineligible for cytotoxic therapy defined by the following:
• a. Age (>/=) 75 years or b. age 18- 74 years with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3 ii. Cardiac history of congestive heart failure requiring treatment or ejection fraction (</=) 50% or chronic stable angina iii. Diffusing capacity of the lungs for carbon monoxide (</=) 65% or forced expiratory volume in the first second of expiration (</=) 65% iv. Creatinine clearance (>/=) 30 mL/min to< 45 mL/min v. any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor before screening and study enrollment.
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Adequate liver and renal function

You may not qualify if…

• Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3 AML)
• Known active central nervous system (CNS) involvement with AML at study entry
• ECOG Performance Status (>/=) 3 in patients who are (>/=) 75 years old or ECOG Performance Status of 4, regardless of age
• 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 arm specific exclusion criteria:
• 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
• 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
• History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
• Received treatment with oral or parenteral anticoagulants/anti-platelet agents within 7 days prior to initiation of study treatment.

Where it is running

• USC Norris Cancer Center — Los Angeles, California, United States
• UC Davis; Comprehensive Cancer Center — Sacramento, California, United States
• Univ of Calif, San Francisco — San Francisco, California, United States
• University of Colorado — Aurora, Colorado, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Weill Cornell Medical College — New York, New York, United States
• Wake Forest Baptist Medical Center — Winston-Salem, North Carolina, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• University of Alberta Hospital — Edmonton, Alberta, Canada
• Princess Margaret Cancer Center — Toronto, Ontario, Canada
• Jewish General Hospital — Montreal, Quebec, Canada
• Hopital Avicenne, Paris — Bobigny, France
• Institut Paoli Calmettes — Marseille, France
• CHU de Bordeaux — Pessac, France
• University of Bologna — Bologna, Emilia-Romagna, Italy
• Presidio san salvatore muraglia — Pesaro, Emilia-Romagna, Italy
• Universita di Roma — Roma, Emilia-Romagna, Italy

Full record on ClinicalTrials.gov

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