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
NCT ID: NCT02670044
Last Updated: 2022-01-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
88 participants
INTERVENTIONAL
2016-03-09
2020-12-10
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Dose Escalation: Arm A (Venetoclax 400mg + Cobi 40mg)
Participants received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm A (Venetoclax 600mg + Cobi 40mg)
Participants received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm A (Venetoclax 800mg + Cobi 40mg)
Participants received Venetoclax 800mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 40mg daily on Days 1-21 of each 28-day treatment cycle.
Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm A (Venetoclax 400mg + Cobi 60mg)
Participants received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Cobimetinib 60mg daily on Days 1-21 of each 28-day treatment cycle.
Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm B (Venetoclax 400mg + Ida 200mg)
Participants received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm B (Venetoclax 600mg + Ida 150mg)
Participants received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 150mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm B (Venetoclax 600mg + Ida 200mg)
Participants received Venetoclax 600mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 200mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Escalation: Arm B (Venetoclax 400mg + Ida 400mg)
Participants received Venetoclax 400mg daily on Days 1-28 of each 28 day treatment cycle and Idasanutlin 400mg daily or twice daily on Days 1-5 of each 28 day treatment cycle.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Dose Optimisation: Arm B (Ven 600mg (Day 1 to 21) + Ida 150mg)
Participants received Venetoclax 600mg daily on Days 1-21 of each 28 day treatment cycle and Idasanutlin 150mg daily on Days 1-5 of each 28 day treatment cycle.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Interventions
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Cobimetinib
Cobimetinib will be administered orally as per schedule in Arm description.
Idasanutlin
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax
Venetoclax will be administered orally as per schedule in Arm description.
Eligibility Criteria
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Inclusion Criteria
* 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
Exclusion Criteria
* 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
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.
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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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
Countries
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References
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Daver NG, Dail M, Garcia JS, Jonas BA, Yee KWL, Kelly KR, Vey N, Assouline S, Roboz GJ, Paolini S, Pollyea DA, Tafuri A, Brandwein JM, Pigneux A, Powell BL, Fenaux P, Olin RL, Visani G, Martinelli G, Onishi M, Wang J, Huang W, Green C, Ott MG, Hong WJ, Konopleva MY, Andreeff M. Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial. Blood. 2023 Mar 16;141(11):1265-1276. doi: 10.1182/blood.2022016362.
Other Identifiers
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2015-003386-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
GH29914
Identifier Type: -
Identifier Source: org_study_id
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