Myeloproliferative Neoplasms Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

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.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

85

Study ID:

NCT04041050

Recruitment Status:

Active, not recruiting

Sponsor:

AbbVie

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There are 42 Locations for this study

See Locations Near You

City of Hope /ID# 239769
Duarte California, 91010, United States
Providence Medical Foundation /ID# 242558
Fullerton California, 92835, United States
Moores Cancer Center at UC San Diego /ID# 229584
La Jolla California, 92093, United States
UCLA /Id# 222784
Los Angeles California, 90095, United States
Northwestern University Feinberg School of Medicine /ID# 224203
Chicago Illinois, 60611, United States
Norton Cancer Institute - St Matthews /ID# 239300
Louisville Kentucky, 40207, United States
Brigitte Harris Cancer Pavilion /ID# 238686
Detroit Michigan, 48202, United States
Onc/Hematology West PC dba Nebraska Cancer Specialists /ID# 242554
Omaha Nebraska, 68130, United States
East Carolina University Brody School of Medicine /ID# 238560
Greenville North Carolina, 27834, United States
Gabrail Cancer Center Research /ID# 228924
Canton Ohio, 44718, United States
Pennsylvania Cancer Specialists Research Institute - Gettysburg /ID# 242550
Gettysburg Pennsylvania, 17325, United States
Virginia Commonwealth University Medical Center Main Hospital /ID# 228169
Richmond Virginia, 23219, United States
UCL Saint-Luc /ID# 225314
Woluwe-Saint-Lambert Bruxelles-Capitale, 1200, Belgium
UMHAT Sveti Georgi /ID# 240022
Plovdiv , 4002, Bulgaria
UMHAT Sveti Ivan Rilski /ID# 240077
Sofia , 1431, Bulgaria
Klinicki bolnicki centar Zagreb /ID# 240140
Zagreb Grad Zagreb, 10000, Croatia
Centre Antoine Lacassagne - Nice /ID# 242293
Nice Alpes-Maritimes, 06189, France
CHU Amiens-Picardie Site Sud /ID# 240792
Amiens CEDEX 1 Somme, 80054, France
AP-HP - Hopital Saint-Louis /ID# 240685
Paris , 75010, France
IUCT Oncopole /ID# 242353
Toulouse Cedex 9 , 31059, France
Universitaetsklinikum Freiburg /ID# 222791
Freiburg Baden-Wuerttemberg, 79106, Germany
Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 224835
Berlin , 13353, Germany
Klinikum Kassel /ID# 225440
Kassel , 34125, Germany
Universitaetsmedizin Rostock /ID# 225436
Rostock , 18057, Germany
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 221408
Rome Lazio, 00168, Italy
ASST Spedali civili di Brescia /ID# 224962
Brescia , 25123, Italy
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS /ID# 224071
Meldola , 47014, Italy
Shonan Kamakura General Hospital /ID# 224315
Kamakura-shi Kanagawa, 247-8, Japan
Kindai University Hospital /ID# 213241
Osakasayama-shi Osaka, 589-8, Japan
Osaka University Hospital /ID# 213235
Suita-shi Osaka, 565-0, Japan
Juntendo University Hospital /ID# 213255
Bunkyo-ku Tokyo, 113-8, Japan
University of Yamanashi Hospital /ID# 229279
Chuo-shi Yamanashi, 409-3, Japan
University Clinical Center Serbia /ID# 240674
Belgrade Beograd, 11000, Serbia
Hospital Duran i Reynals /ID# 224007
Hospitalet de Llobregat Barcelona, 08907, Spain
CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 224839
Pamplona Navarra, 31008, Spain
CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 226041
Madrid , 28027, Spain
Linkoping University Hospital /ID# 239995
Linkoping , 581 8, Sweden
Karolinska University Hospital /ID# 239992
Stockholm , 141 8, Sweden
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 215631
Kaohsiung , 807, Taiwan
China Medical University Hospital /ID# 215634
Taichung City , 40447, Taiwan
Dokuz Eylul University Medical Faculty /ID# 239952
Izmir , 35340, Turkey
Gloucestershire Hospitals NHS Foundation Trust /ID# 241189
Cheltenham Gloucestershire, GL53 , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

85

Study ID:

NCT04041050

Recruitment Status:

Active, not recruiting

Sponsor:


AbbVie

How clear is this clinincal trial information?

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