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Clinical Trials in the USA / NCT04041050
Active, not recruiting Phase 1

A Study Evaluating Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm

NCT04041050 · tracked via the Priya Life Science USA tracker
Sponsor
AbbVie
Phase
Phase 1
Started
2019-11-08
Last updated
2025-02-14

Condition(s) studied

Myeloproliferative Neoplasm

Investigational drug(s) / intervention(s)

NavitoclaxRuxolitinibCelecoxib

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

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: Parts 1 and 2: * Navitoclax Monotherapy (Part 1 Only - Japanese Participants): * Documented diagnosis of myelofibrosis (MF), polycythemia vera (PV) or essential thrombocythemia (ET) as defined by the World Health Organization (WHO) classification. * MF participants must have received and failed or are intolerant to ruxolitinib therapy. * ET or PV participants must be requiring cytoreduction who have failed or are intolerant to at least one prior therapy, or who refuse standard therapy. * Navitoclax + ruxolitinib Combination Therapy (Part 2 Only - Japanese and Taiwanese Participants): * Has documented diagnosis of primary MF, post-polycythemia vera MF (PPV-MF), or post-essential thrombocythemia (PET-MF) as defined by the World Health Organization (WHO) classification. * Is ineligible or unwilling to undergo stem cell transplantation at time of study entry. * Has splenomegaly as defined by a spleen palpable \>= 5 cm below costal margin or spleen volume \>= 450 cm\^3 as assessed by magnetic resonance imaging (MRI) or computed topography (CT) scan. * Must have received ruxolitinib therapy for at least 12 weeks and be currently on a stable dose of ruxolitinib (as described in the protocol). * Must have adequate bone marrow, kidney, liver and hematology blood values as detailed in the study protocol. * Part 1 only: Cytoreduction for participants with ET and PV therapy within 14 days prior to the first dose of navitoclax will be allowed pending additional discussion with study doctor. Ruxolitinib for MF participants will not be allowed within 7 days prior to the first dose of study drug and during navitoclax administration. * Eastern Cooperative Oncology Group (ECOG) performance status \<= 1. Part 3, and Part 4 (Participants in US and Europe): * Part 3 Only: At screening or baseline (pre-dose on Day 1), participant has QT interval corrected for heart rate (QTc) interval by Fridericia's correction (QTcF) \<= 450 msec. * Participants with a documented diagnosis of primary or secondary MF, ET, PV or chronic myelomonocytic leukemia (CMML) as defined by the WHO classification. * Participants must be requiring treatment and have failed or are intolerant to at least one prior therapy or who refuse standard therapy. * ECOG performance status \<= 2. * Must have adequate bone marrow, kidney, liver and hematology blood values as detailed in the study protocol. Part 5 (Participants in US and Europe): * Has a documented diagnosis of primary MF as defined by the WHO classification, post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF. * Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System (DIPSS). * Requiring treatment for MF and must either have no prior treatment with a JAK2 inhibitor or have received treatment with ruxolitinib as noted in the protocol. * Have an ECOG performance status \<=2. * Have adequate bone marrow, kidney, liver and hematology blood values as detailed in the protocol. Exclusion Criteria: Part 1 and 2: * Shows leukemic transformation (\> 10% blasts in peripheral blood or bone marrow biopsy). * Has a history of an active malignancy other than MPN within the past 2 years prior to study entry (exceptions detailed in the protocol). * Has a positive test result for HIV at screening. * Has chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. * Has evidence of other clinically significant uncontrolled condition(s). * Has previously taken a BH3 mimetic compound. * Currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and low-molecular-weight heparin (LMWH). * Has received strong or moderate CYP3A inhibitors (e.g., ketoconazole, clarithromycin) within 14 days prior to the administration of the first dose of navitoclax. Part 3, and Part 4: * Had prior therapy with a BH3 mimetic compound. * Have received strong or moderate CYP3A inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of navitoclax. * Have received strong CYP3A inducers within 10 days prior to the first dose of navitoclax. * Show leukemic transformation (\> 10% blasts in peripheral blood or bone marrow biopsy). * Currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH. Part 4 Only: * Have received CYP2C9 inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs. * Have received CYP2C9 inducers within 10 days prior to the first dose of study drugs. Part 5 Only: * Have accelerated MF, defined as \> 10% blasts in peripheral blood or bone marrow aspirate and biopsy. * Eligible for stem cell transplantation at time of study entry. * Had prior therapy with a BH3 mimetic compound or BET inhibitor. * Currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH. * Have received strong CYP3A inhibitors or CYP2C9 inhibitors within 28 days of 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs. * Have received strong CYP3A inducers or CYP2C9 inducers within 10 days prior to the first dose of study drugs.

Primary outcome measure(s)

Trial sites (42)

FacilityCityRegionStatus
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

📄 Jakafi (ruxolitinib) drug profile →

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Official registry record

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 the USA