A Study Evaluating Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm
Condition(s) studied
Investigational drug(s) / intervention(s)
Navitoclax: Tablet; Oral
Ruxolitinib: Tablet; Oral
Celecoxib: Capsule; Oral
Study summary
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.
Eligibility
Primary outcome measure(s)
- Number of Participants with Dose Limiting Toxicities (DLT) (Part 1 and Part 2) — Up to 28 days after the navitoclax initiation
Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 28-day cycle of navitoclax. - Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Part 2 and 5) — Up to approximately 1 day
Maximum Observed Plasma Concentration (Cmax) of Navitoclax. - Maximum Observed Plasma Concentration (Cmax) of Celecoxib (Part 4) — Up to approximately 1 day
Maximum Observed Plasma Concentration (Cmax) of Celecoxib. - Time to Cmax (peak time, Tmax) of Navitoclax (Part 2 and 5) — Up to approximately 1 day
Tmax defined as time to maximum observed plasma concentration of Navitoclax. - Time to Cmax (peak time, Tmax) of Celecoxib (Part 4) — Up to approximately 1 day
Tmax defined as time to maximum observed plasma concentration of Celecoxib. - Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Navitoclax — Up to approximately 2 days
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Navitoclax. - Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Celecoxib (Part 4) — Up to approximately 2 days
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Celecoxib. - Number of Participants with Adverse Events — From first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).
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. - Change in QT interval corrected for heart rate interval by Fridericia's correction formula (QTcF) (Part 3) — From first dose of study drug until 30 days following last dose of study drug.
Change in QTcF (Part 3).
Trial sites (42)
| Facility | City | Region | Status |
|---|---|---|---|
| City of Hope /ID# 239769 | Duarte | California | |
| Providence - St. Jude Medical Center /ID# 242558 | Fullerton | California | |
| Moores Cancer Center at UC San Diego /ID# 229584 | La Jolla | California | |
| UCLA /Id# 222784 | Los Angeles | California | |
| Northwestern University Feinberg School of Medicine /ID# 224203 | Chicago | Illinois | |
| Norton Cancer Institute - St. Matthews /ID# 239300 | Louisville | Kentucky | |
| Duplicate_Brigitte Harris Cancer Pavilion /ID# 238686 | Detroit | Michigan | |
| Nebraska Cancer Specialists - Omaha - Wright Street /ID# 242554 | Omaha | Nebraska | |
| Duplicate_East Carolina University Brody School of Medicine /ID# 238560 | Greenville | North Carolina | |
| Gabrail Cancer Center Research /ID# 228924 | Canton | Ohio | |
| Pennsylvania Cancer Specialists Research Institute - Gettysburg /ID# 242550 | Gettysburg | Pennsylvania | |
| Virginia Commonwealth University Medical Center Main Hospital /ID# 228169 | Richmond | Virginia | |
| Cliniques Universitaires UCL Saint-Luc /ID# 225314 | Woluwe-Saint-Lambert | Brussels Capital | |
| UMHAT Sveti Georgi /ID# 240022 | Plovdiv | Bulgaria | |
| UMHAT Sveti Ivan Rilski /ID# 240077 | Sofia | Bulgaria | |
| Klinicki bolnicki centar Zagreb /ID# 240140 | Zagreb | City of Zagreb | |
| Centre Antoine Lacassagne - Nice /ID# 242293 | Nice | Alpes-Maritimes | |
| CHU Amiens-Picardie Site Sud /ID# 240792 | Amiens | Somme | |
| AP-HP - Hopital Saint-Louis /ID# 240685 | Paris | France | |
| IUCT Oncopole /ID# 242353 | Toulouse | France | |
| Universitaetsklinikum Freiburg /ID# 222791 | Freiburg im Breisgau | Baden-Wurttemberg | |
| Klinikum Kassel /ID# 225440 | Kassel | Hesse | |
| Universitaetsmedizin Rostock /ID# 225436 | Rostock | Mecklenburg-Vorpommern | |
| Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 224835 | Berlin | Germany | |
| Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita Cattolica /ID# 221408 | Rome | Lazio | |
| ASST Spedali civili di Brescia /ID# 224962 | Brescia | Italy | |
| Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS /ID# 224071 | Meldola | Italy | |
| Shonan Kamakura General Hospital /ID# 224315 | Kamakura-shi | Kanagawa | |
| Kindai University Hospital /ID# 213241 | Osakasayama-shi | Osaka | |
| Osaka University Hospital /ID# 213235 | Suita-shi | Osaka | |
| Juntendo University Hospital /ID# 213255 | Bunkyo-ku | Tokyo | |
| University of Yamanashi Hospital /ID# 229279 | Chuo-shi | Yamanashi | |
| University Clinical Center Serbia /ID# 240674 | Belgrade | Beograd | |
| Hospital Duran i Reynals /ID# 224007 | L'Hospitalet de Llobregat | Barcelona | |
| Clinica Universidad de Navarra - Pamplona /ID# 224839 | Pamplona | Navarre | |
| CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 226041 | Madrid | Spain | |
| Duplicate_Karolinska University Hospital /ID# 239992 | Stockholm | Stockholm County | |
| Linkoping University Hospital /ID# 239995 | Linköping | Sweden | |
| Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 215631 | Kaohsiung City | Taiwan | |
| China Medical University Hospital /ID# 215634 | Taichung | Taiwan |
+ 2 more sites — see the full list on the official registry below.
On this site
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT04041050 on ClinicalTrials.gov ↗ ← All trials in Spain