There are 5 parts to this study for which the primary objectives are to evaluate safety, tolerability, and pharmacokinetics (PK) of navitoclax when administered alone (Part 1) or when administered in combination with ruxolitinib (Part 2). In Part 2, participants must have been receiving a stable dose of ruxolitinib therapy for at least 12 weeks prior to study enrollment. In Part 3, all eligible participants will receive navitoclax, with the primary objective being to evaluate potential navitoclax effect on QTc prolongation. In Part 4, effect of navitoclax is evaluated on the PK, safety, and tolerability of a single dose of celecoxib. In Part 5, all eligible participants will receive ruxolitinib twice daily and navitoclax once daily for drug-drug interaction (DDI) assessment, followed by continued administration of navitoclax in combination with ruxolitinib.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
Tablet; Oral
Tablet; Oral
Capsule; Oral
City of Hope /ID# 239769
Duarte, California, United States
Providence - St. Jude Medical Center /ID# 242558
Fullerton, California, United States
Moores Cancer Center at UC San Diego /ID# 229584
La Jolla, California, United States
UCLA /Id# 222784
Los Angeles, California, United States
Northwestern University Feinberg School of Medicine /ID# 224203
Chicago, Illinois, United States
Number of Participants with Dose Limiting Toxicities (DLT) (Part 1 and Part 2)
Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 28-day cycle of navitoclax.
Time frame: Up to 28 days after the navitoclax initiation
Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Part 2 and 5)
Maximum Observed Plasma Concentration (Cmax) of Navitoclax.
Time frame: Up to approximately 1 day
Maximum Observed Plasma Concentration (Cmax) of Celecoxib (Part 4)
Maximum Observed Plasma Concentration (Cmax) of Celecoxib.
Time frame: Up to approximately 1 day
Time to Cmax (peak time, Tmax) of Navitoclax (Part 2 and 5)
Tmax defined as time to maximum observed plasma concentration of Navitoclax.
Time frame: Up to approximately 1 day
Time to Cmax (peak time, Tmax) of Celecoxib (Part 4)
Tmax defined as time to maximum observed plasma concentration of Celecoxib.
Time frame: Up to approximately 1 day
Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Navitoclax
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Navitoclax.
Time frame: Up to approximately 2 days
Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Celecoxib (Part 4)
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Celecoxib.
Time frame: Up to approximately 2 days
Number of Participants with Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Time frame: From first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).
Change in QT interval corrected for heart rate interval by Fridericia's correction formula (QTcF) (Part 3)
Change in QTcF (Part 3).
Time frame: From first dose of study drug until 30 days following last dose of study drug.
Overall Response Rate
ORR according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment/European Leukemia Net (IWG-MRT/ELN) criteria for participants with myelofibrosis, essential thrombocythemia, and polycythemia vera, and according to IWG criteria for participants with CMML.
Time frame: Up to approximately 96 weeks
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Norton Cancer Institute - St. Matthews /ID# 239300
Louisville, Kentucky, United States
Duplicate_Brigitte Harris Cancer Pavilion /ID# 238686
Detroit, Michigan, United States
Nebraska Cancer Specialists - Omaha - Wright Street /ID# 242554
Omaha, Nebraska, United States
Duplicate_East Carolina University Brody School of Medicine /ID# 238560
Greenville, North Carolina, United States
Gabrail Cancer Center Research /ID# 228924
Canton, Ohio, United States
...and 32 more locations