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Myeloproliferative NeoplasmPhase 1NCT04041050

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

A Phase 1 study testing Navitoclax, Ruxolitinib and Celecoxib in people with Myeloproliferative Neoplasm, run by AbbVie at 42 sites in 14 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myeloproliferative Neoplasm
What is being tested?
Navitoclax, Ruxolitinib and Celecoxib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
42 sitesin 14 countries
Study dates
8 Nov 2019to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

42 sites in 14 countries.

42 sites in 14 countries

United States12 sites

  • Gabrail Cancer Center Research /ID# 228924

    Canton, Ohio, 44718

  • Northwestern University Feinberg School of Medicine /ID# 224203

    Chicago, Illinois, 60611-2927

  • Duplicate_Brigitte Harris Cancer Pavilion /ID# 238686

    Detroit, Michigan, 48202-2610

  • City of Hope /ID# 239769

    Duarte, California, 91010

  • Providence - St. Jude Medical Center /ID# 242558

    Fullerton, California, 92835

  • Pennsylvania Cancer Specialists Research Institute - Gettysburg /ID# 242550

    Gettysburg, Pennsylvania, 17325

  • Duplicate_East Carolina University Brody School of Medicine /ID# 238560

    Greenville, North Carolina, 27834

  • Moores Cancer Center at UC San Diego /ID# 229584

    La Jolla, California, 92093

  • UCLA /Id# 222784

    Los Angeles, California, 90095-1678

  • Norton Cancer Institute - St. Matthews /ID# 239300

    Louisville, Kentucky, 40207

  • Nebraska Cancer Specialists - Omaha - Wright Street /ID# 242554

    Omaha, Nebraska, 68130

  • Virginia Commonwealth University Medical Center Main Hospital /ID# 228169

    Richmond, Virginia, 23219

Other trials in United States

Japan5 sites

  • Juntendo University Hospital /ID# 213255

    Bunkyo-ku, Tokyo, 113-8431

  • University of Yamanashi Hospital /ID# 229279

    Chuo-shi, Yamanashi, 409-3821

  • Shonan Kamakura General Hospital /ID# 224315

    Kamakura-shi, Kanagawa, 247-8533

  • Kindai University Hospital /ID# 213241

    Osakasayama-shi, Osaka, 589-8511

  • Osaka University Hospital /ID# 213235

    Suita-shi, Osaka, 565-0871

Other trials in Japan

France4 sites

  • CHU Amiens-Picardie Site Sud /ID# 240792

    Amiens, Somme, 80054

  • Centre Antoine Lacassagne - Nice /ID# 242293

    Nice, Alpes-Maritimes, 06189

  • AP-HP - Hopital Saint-Louis /ID# 240685

    Paris, 75010

  • IUCT Oncopole /ID# 242353

    Toulouse, 31059

Other trials in France

Germany4 sites

  • Charite Universitaetsklinikum Berlin - Campus Virchow /ID# 224835

    Berlin, 13353

  • Universitaetsklinikum Freiburg /ID# 222791

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Klinikum Kassel /ID# 225440

    Kassel, Hesse, 34125

  • Universitaetsmedizin Rostock /ID# 225436

    Rostock, Mecklenburg-Vorpommern, 18057

Other trials in Germany

Italy3 sites

  • ASST Spedali civili di Brescia /ID# 224962

    Brescia, 25123

  • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS /ID# 224071

    Meldola, 47014

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Universita Cattolica /ID# 221408

    Rome, Lazio, 00168

Other trials in Italy

Spain3 sites

  • Hospital Duran i Reynals /ID# 224007

    L'Hospitalet de Llobregat, Barcelona, 08907

  • CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 226041

    Madrid, 28027

  • Clinica Universidad de Navarra - Pamplona /ID# 224839

    Pamplona, Navarre, 31008

Other trials in Spain

Bulgaria2 sites

  • UMHAT Sveti Georgi /ID# 240022

    Plovdiv, 4002

  • UMHAT Sveti Ivan Rilski /ID# 240077

    Sofia, 1431

Other trials in Bulgaria

Sweden2 sites

  • Linkoping University Hospital /ID# 239995

    Linköping, 581 85

  • Duplicate_Karolinska University Hospital /ID# 239992

    Stockholm, Stockholm County, 141 86

Other trials in Sweden

Taiwan2 sites

  • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 215631

    Kaohsiung City, 807

  • China Medical University Hospital /ID# 215634

    Taichung, 40447

Other trials in Taiwan

Belgium1 site

  • Cliniques Universitaires UCL Saint-Luc /ID# 225314

    Woluwe-Saint-Lambert, Brussels Capital, 1200

Other trials in Belgium

Croatia1 site

  • Klinicki bolnicki centar Zagreb /ID# 240140

    Zagreb, City of Zagreb, 10000

Other trials in Croatia

Serbia1 site

  • University Clinical Center Serbia /ID# 240674

    Belgrade, Beograd, 11000

Other trials in Serbia

Turkey (Türkiye)1 site

  • Dokuz Eylul University Medical Faculty /ID# 239952

    Izmir, 35340

Other trials in Turkey (Türkiye)

United Kingdom1 site

  • Gloucestershire Hospitals NHS Foundation Trust /ID# 241189

    Cheltenham, Gloucestershire, GL53 7AN

Other trials in United Kingdom

About this study

Official title: A Phase 1 Open-Label Study Evaluating the Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Myeloproliferative Neoplasm Subjects

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.

Being tested
Navitoclax, Ruxolitinib, Celecoxib
Keywords
Myeloproliferative Neoplasm (MPN), Chronic myelomonocytic leukemia (CMML), Polycythemia Vera (PV), Essential Thrombocythemia (ET), Myelofibrosis (MF), cancer, navitoclax, ruxolitinib
Medical subject headings
Myeloproliferative Disorders, Leukemia, Myelomonocytic, Chronic, Polycythemia Vera, Thrombocythemia, Essential, Primary Myelofibrosis, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NavitoclaxDrug

    Also called ABT-263

    Tablet; Oral

  • RuxolitinibDrug

    Tablet; Oral

  • CelecoxibDrug

    Also called Celebrex

    Capsule; Oral

Study groups in NCT04041050
Study groupRoleWhat they receive
Part 1: Navitoclax MonotherapyExperimentalParticipants will receive various doses of navitoclax once daily (QD).
Receives: Drug: Navitoclax
Part 2: Navitoclax + Ruxolitinib Combination TherapyExperimentalParticipants will receive various doses of navitoclax once daily (QD) in combination with ruxolitinib twice daily (BID).
Receives: Drug: Navitoclax; Drug: Ruxolitinib
Part 3: Navitoclax MonotherapyExperimentalParticipants will receive navitoclax once daily (QD).
Receives: Drug: Navitoclax
Part 4: Navitoclax + CelecoxibExperimentalParticipants will receive navitoclax once daily (QD) starting on Day 3. Participants will also receive celecoxib single dose on Day 1 and Day 7.
Receives: Drug: Navitoclax; Drug: Celecoxib
Part 5: Navitoclax + Ruxolitinib Combination TherapyExperimentalParticipants will receive ruxolitinib BID and navitoclax QD for drug-drug interaction (DDI) assessment, followed by continued administration of navitoclax in combination with ruxolitinib.
Receives: Drug: Navitoclax; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 28 days after the navitoclax initiation

  2. Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Part 2 and 5)

    Maximum Observed Plasma Concentration (Cmax) of Navitoclax.

    Measured: Up to approximately 1 day

  3. Maximum Observed Plasma Concentration (Cmax) of Celecoxib (Part 4)

    Maximum Observed Plasma Concentration (Cmax) of Celecoxib.

    Measured: Up to approximately 1 day

  4. Time to Cmax (peak time, Tmax) of Navitoclax (Part 2 and 5)

    Tmax defined as time to maximum observed plasma concentration of Navitoclax.

    Measured: Up to approximately 1 day

  5. Time to Cmax (peak time, Tmax) of Celecoxib (Part 4)

    Tmax defined as time to maximum observed plasma concentration of Celecoxib.

    Measured: Up to approximately 1 day

  6. 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.

    Measured: Up to approximately 2 days

  7. 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.

    Measured: Up to approximately 2 days

  8. 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.

    Measured: From first dose of study drug until 30 days following last dose of study drug (up to approximately 5 years).

  9. Change in QT interval corrected for heart rate interval by Fridericia's correction formula (QTcF) (Part 3)

    Change in QTcF (Part 3).

    Measured: From first dose of study drug until 30 days following last dose of study drug.

Secondary outcomes (1)

  1. 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.

    Measured: Up to approximately 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2019
  2. Study start8 Nov 2019
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
85 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04041050
Sponsor's protocol ID
M19-753
Other IDs
2020-002597-27
Status last verified
Jun 2024
First submitted
30 Jul 2019
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Navitoclax, Ruxolitinib and Celecoxib in people with Myeloproliferative Neoplasm, run by AbbVie at 42 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States, Japan, France, Germany, Italy and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with Dose Limiting Toxicities (DLT) (Part 1 and Part 2) (time frame: Up to 28 days after the navitoclax initiation). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04041050.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2025.

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