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Myelofibrosis (MF)Phase 1NCT04454658

Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis

A Phase 1 study testing ABBV-744, Navitoclax and Ruxolitinib in people with Myelofibrosis (MF), run by AbbVie at 43 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

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis (MF)
What is being tested?
ABBV-744, Navitoclax and Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
43 sitesin 14 countries
Study dates
11 Nov 2020to Jan 2027
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

  • Laboratory values indicative of adequate bone marrow, renal, and hepatic function meeting protocol criteria.
  • Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of the 7 days prior to Day 1 with at least 2 symptoms with a score >=3 or a total score of >=10.
  • Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocytopenia MF (PET-MF) as defined by the World Health Organization (WHO).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 2.
  • Intermediate - 2, or High-Risk disease as defined by the Dynamic International Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable splenomegaly >=5 centimeters [cm] below costal margin are also eligible).
  • Splenomegaly defined as spleen palpation measurement >= 5 cm below costal margin or spleen volume >= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and C, baseline spleen assessment must be obtained > 7 days after discontinuation of most recent Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days of Cycle 1 Day 1).
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  • Segment-Specific Prior Therapy Criteria:
  • Segment A:
  • Prior exposure to one or more Janus Kinase inhibitors (JAKi),[the most recent of which was discontinued > 14 days prior to Cycle 1 Day 1] and are intolerant, resistant, refractory or lost response to the JAKi.
  • Segment B:
  • Currently receiving ruxolitinib AND
  • Willingness to reduce ruxolitinib dose (if on a higher dose); and on a stable dose for 14 days or longer prior to Cycle 1 Day 1; AND
  • At least one of the following criteria (a, b, or c):
  • >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib therapy;
  • < 24 weeks duration of current ruxolitinib course with documented resistance, refractories, or loss of response, as defined by any of the following:
  • Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM), in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
  • >=100% increase in the palpable distance below the LCM, in participants with measurable spleen distance 5 - 10 cm prior to the initiation of ruxolitinib.
  • >=50% increase in the palpable distance below the LCM, in participants with measurable spleen > 10 cm prior to the initiation of ruxolitinib.
  • A spleen volume increase >= 25% (as assessed by MRI or CT) in participants with a spleen volume assessment available prior to the initiation of ruxolitinib.
  • Prior treatment with ruxolitinib for >= 28 days complicated by any of the following:
  • Development of red blood cell transfusion requirement (at least 2 units/month for 2 months).
  • Grade >= 3 adverse events of neutropenia and/or anemia while on ruxolitinib treatment, with improvement or resolution upon dose reduction.
  • Segment C:
  • Prior exposure to one or more JAKi (the most recent of which was discontinued > 14 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or lost response to the JAKi.

Who cannot join

  • Segment-Specific Prior Therapy Criteria:
  • Segment A:
  • Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors.
  • Segment B:
  • Prior exposure to one or more BET inhibitors.
  • Segment C:
Show all 9Show fewer
  • Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL)-2 and/or BCL- XL inhibitor, including navitoclax.
  • Segment D:
  • Prior exposure to JAKi and/or any BET inhibitor.

Trial locations and contacts

43 sites in 14 countries.

43 sites in 14 countries

United States10 sites

  • Roswell Park Cancer Institute /ID# 222557

    Buffalo, New York, 14263

  • Gabrail Cancer Center Research /ID# 222802

    Canton, Ohio, 44718

  • Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004

    Dallas, Texas, 75246-2003

  • Duplicate_Dartmouth-Hitchcock Medical Center - 1 Medical Center Drive /ID# 224623

    Lebanon, New Hampshire, 03756

  • The Mount Sinai Hospital /ID# 221549

    New York, New York, 10029

  • Weill Cornell Medical College /ID# 227069

    New York, New York, 10065

  • University of Oklahoma, Stephenson Cancer Center /ID# 224095

    Oklahoma City, Oklahoma, 73104-5418

  • Oregon Health and Science University /ID# 221801

    Portland, Oregon, 97239

  • University of California, Davis Comprehensive Cancer Center /ID# 221790

    Sacramento, California, 95817

  • VA Puget Sound Health Care System /ID# 224208

    Seattle, Washington, 98108-1597

Other trials in United States

Brazil6 sites

  • Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636

    Goiânia, Goiás, 74605-020

  • Hospital de Clinicas de Porto Alegre /ID# 226635

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Instituto Nacional de Cancer (INCA) /ID# 226637

    Rio de Janeiro, 20231-050

  • Duplicate_Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640

    São Paulo, São Paulo, 05652-900

  • Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641

    São Paulo, 01323-001

  • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 226639

    São Paulo, 05403-000

Other trials in Brazil

Japan4 sites

  • University of Yamanashi Hospital /ID# 225503

    Chuo-shi, Yamanashi, 409-3821

  • Kyushu University Hospital /ID# 228035

    Fukuoka, Fukuoka, 812-8582

  • Osaka Metropolitan University Hospital /ID# 225502

    Osaka, Osaka, 545-8586

  • Duplicate_Hokkaido University Hospital /ID# 228038

    Sapporo, Hokkaido, 060-8648

Other trials in Japan

Australia3 sites

  • Townsville University Hospital /ID# 225859

    Douglas, Queensland, 4814

  • Royal Hobart Hospital /ID# 241677

    Hobart, Tasmania, 7000

  • Royal Perth Hospital /ID# 241678

    Perth, Western Australia, 6000

Other trials in Australia

Chile3 sites

  • Icegclinic /Id# 231086

    La Florida, Santiago Metropolitan, 8241479

  • Fundacion Arturo Lopez Perez /ID# 225037

    Providencia, Santiago Metropolitan, 7500921

  • Duplicate_Sociedad de Investigaciones Médicas Limitada /ID# 224175

    Temuco, Araucania, 4810469

Other trials in Chile

Israel3 sites

  • Hadassah Medical Center-Hebrew University /ID# 243852

    Jerusalem, Jerusalem, 91120

  • The Chaim Sheba Medical Center /ID# 222151

    Ramat Gan, Tel Aviv, 5265601

  • Tel Aviv Sourasky Medical Center /ID# 223548

    Tel Aviv, Tel Aviv, 6423906

Other trials in Israel

Argentina2 sites

  • Hospital Italiano de Buenos Aires /ID# 226945

    Ciudad Autonoma Buenos Aires, Buenos Aires F.D., 1199

  • Hospital Universitario Austral /ID# 228909

    Pilar, Buenos Aires, 1629

Other trials in Argentina

Bulgaria2 sites

  • SHAT Hematologic Diseases /ID# 226007

    Sofia, 1797

  • UMHAT Sveta Marina /ID# 226681

    Varna, 9010

Other trials in Bulgaria

Hungary2 sites

  • Duplicate_Semmelweis Egyetem /ID# 224085

    Budapest, 1085

  • Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249

    Gyöngyös, Heves County, 3200

Other trials in Hungary

Spain2 sites

  • Hospital Santa Creu i Sant Pau /ID# 238501

    Barcelona, 08041

  • Hospital General Universitario Gregorio Maranon /ID# 233279

    Madrid, 28007

Other trials in Spain

Sweden2 sites

  • Orebro Universitetssjukhuset /ID# 228514

    Örebro, Örebro County, 701 85

  • Akademiska Sjukhuset /ID# 228515

    Uppsala, Uppsala County, 751 85

Other trials in Sweden

Turkey (Türkiye)2 sites

  • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 234215

    Ankara, 06200

  • Koc Universitesi Hastanesi Translasyonel Tıp Arastırma Merkezi /ID# 234214

    Istanbul, 34010

Other trials in Turkey (Türkiye)

Italy1 site

  • Duplicate_Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397

    Milan, Milano, 20122

Other trials in Italy

South Korea1 site

  • Duplicate_Inje University Busan Paik Hospital /ID# 233707

    Busan, Busan Gwang Yeogsi, 47392

Other trials in South Korea

About this study

Official title: A Phase 1b Study Of ABBV-744 Alone Or In Combination With Ruxolitinib Or Navitoclax In Subjects With Myelofibrosis

Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to see how safe and tolerable ABBV-744 is, when given alone, and in combination with ruxolitinib or navitoclax, for adult participants with MF.

ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.

Read more

In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet to identify safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744 and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.

Being tested
ABBV-744, Navitoclax, Ruxolitinib
Keywords
ABBV-744, Navitoclax, Ruxolitinib, ABT-263, Cancer, Myelofibrosis, MF
Medical subject headings
Primary Myelofibrosis, Neoplasms

What participants receive

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

  • ABBV-744Drug

    Tablet; Oral

  • NavitoclaxDrug

    Also called ABT-263

    Tablet; Oral

  • RuxolitinibDrug

    Tablet; Oral

Study groups in NCT04454658
Study groupRoleWhat they receive
Segment A: ABBV-744 Dose Identification and OptimizationExperimentalParticipants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.
Receives: Drug: ABBV-744
Segment A: ABBV-744 MonotherapyExperimentalParticipants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.
Receives: Drug: ABBV-744
Segment B: Ruxolitinib + ABBV-744 "Add on" TherapyExperimentalParticipants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.
Receives: Drug: ABBV-744; Drug: Ruxolitinib
Segment C: ABBV-744 + NavitoclaxExperimentalParticipants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.
Receives: Drug: ABBV-744; Drug: Navitoclax
Segment D: ABBV-744 + RuxolitinibExperimentalParticipants who have never received JAKi will receive ABBV-744 and ruxolitinib.
Receives: Drug: ABBV-744; Drug: Ruxolitinib

What is being measured

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

  1. Percentage of Participants With Adverse Events

    An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug.

    Measured: Up to Approximately 1 year from start of study

Secondary outcomes (16)

  1. Percentage Of Participants Who Achieve Spleen Volume Reduction Of 35% Or Greater (SVR35)

    Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan.

    Measured: Up To Week 24

  2. Maximum Observed Plasma Concentration (Cmax) of ABBV-744

    Maximum observed plasma concentration (Cmax) of ABBV-744.

    Measured: Up To Week 12

  3. Time To Cmax (Tmax) Of ABBV-744

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  4. Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744

    AUC of ABBV-744 will be calculated.

    Measured: Up To Week 12

  5. Half-Life (t1/2) Of ABBV-744

    Half-life of ABBV-744 will be calculated.

    Measured: Up To Week 12

  6. Accumulation Ratio Of ABBV-744

    Pharmacokinetic parameters will include accumulation ratio of ABBV-744.

    Measured: Up To Week 12

  7. Apparent Clearance (CL/F) Of ABBV-744

    CL/F of ABBV-744 will be calculated.

    Measured: Up To Week 12

  8. Apparent Volume Of Distribution (Vd/F) Of ABBV-744

    Vd/F of ABBV-744 will be calculated.

    Measured: Up To Week 12

  9. Percentage Of Participants With >= 50% Reduction In Total Symptom Score (TSS)

    TSS is assessed using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. MFSAF v4.0 measures the burden of myelofibrosis-related symptoms. The symptoms are assessed on a 11-point numeric rating scale (NRS) anchored from 0 (absent) to 10 (worst imaginable).

    Measured: Up to Week 24

  10. Objective Response Rate (ORR)

    ORR is defined as the sum of rates of partial remission (PR) or better.

    Measured: Week 24

  11. Maximum Observed Plasma Concentration (Cmax) Of Navitoclax

    Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.

    Measured: Up To Week 12

  12. Time To Cmax (Tmax) Of Navitoclax

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  13. Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax

    AUC of Navitoclax will be calculated.

    Measured: Up To Week 12

  14. Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib

    Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.

    Measured: Up To Week 12

  15. Time To Cmax (Tmax) Of Ruxolitinib

    The amount of time taken to reach Cmax.

    Measured: Up To Week 12

  16. Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib

    AUC of Ruxolitinib will be calculated.

    Measured: Up To Week 12

Timeline

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

  1. First posted1 Jul 2020
  2. Study start11 Nov 2020
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2027 (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
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04454658
Sponsor's protocol ID
M20-247
Other IDs
2020-001225-32
Status last verified
Jul 2025
First submitted
30 Jun 2020
Last updated
16 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mascarenhas J, Fogliatto L, Green S, Corvalan I, Traer E, Kirito K, Chuah H, Sakatoku K, Hoeg R, Khawandanah M, Lavie D, Hunter Z, Quinn D, Wang Y, Harb J, Zha J, Malyankar U, Ritchie E. Phase 1b study of ABBV-744, a novel, selective BET inhibitor, as monotherapy for patients with myelofibrosis. Blood Adv. 2026 May 26;10(10):3543-3553. doi: 10.1182/bloodadvances.2025018695.

    PubMed 41843794

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ABBV-744, Navitoclax and Ruxolitinib in people with Myelofibrosis (MF), run by AbbVie at 43 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 24 inclusion and 9 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 16 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 43 sites in United States, Brazil, Japan, Australia, Chile 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?

Percentage of Participants With Adverse Events (time frame: Up to Approximately 1 year from start of study). 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 NCT04454658, which also lists 1 linked publication.

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 16 Jul 2025.

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