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 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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelofibrosis (MF)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Navitoclax; Drug: ABBV-744

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, 1629
      • Hospital Universitario Austral /ID# 228909
  • Ciudad Autonoma De Buenos Aires
    • Ciudad Autonoma Buenos Aires, Ciudad Autonoma De Buenos Aires, Argentina, 1199
      • Hospital Italiano de Buenos Aires /ID# 226945
• Australia
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville University Hospital /ID# 225859
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital /ID# 241677
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 241678
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
    • Instituto Nacional de Cancer (INCA) /ID# 226637
  • Sao Paulo, Brazil, 01323-001
    • Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641
  • Sao Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 226639
  • Goias
    • Goiania, Goias, Brazil, 74605-020
      • Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre /ID# 226635
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05652-900
      • Duplicate_Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640
• Bulgaria
  • Sofia, Bulgaria, 1797
    • SHAT Hematologic Diseases /ID# 226007
  • Varna, Bulgaria, 9010
    • UMHAT Sveta Marina /ID# 226681
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4810469
      • Duplicate_Sociedad de Investigaciones Médicas Limitada /ID# 224175
  • Region Metropolitana De Santiago
    • La Florida, Region Metropolitana De Santiago, Chile, 8241479
      • Icegclinic /Id# 231086
    • Providencia, Region Metropolitana De Santiago, Chile, 7500921
      • Fundacion Arturo Lopez Perez /ID# 225037
• Hungary
  • Budapest, Hungary, 1085
    • Duplicate_Semmelweis Egyetem /ID# 224085
  • Heves
    • Gyongyos, Heves, Hungary, 3200
      • Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249
• Israel
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 222151
    • Tel Aviv, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 223548
  • Yerushalayim
    • Jerusalem, Yerushalayim, Israel, 91120
      • Hadassah Medical Center-Hebrew University /ID# 243852
• Italy
  • Milano
    • Milan, Milano, Italy, 20122
      • Duplicate_Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397
• Japan
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 228035
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 060-8648
      • Duplicate_Hokkaido University Hospital /ID# 228038
  • Osaka
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka Metropolitan University Hospital /ID# 225502
  • Yamanashi
    • Chuo-shi, Yamanashi, Japan, 409-3821
      • University of Yamanashi Hospital /ID# 225503
• Korea, Republic of
  • Busan Gwang Yeogsi
    • Busan, Busan Gwang Yeogsi, Korea, Republic of, 47392
      • Duplicate_Inje University Busan Paik Hospital /ID# 233707
• Spain
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau /ID# 238501
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 233279
• Sweden
  • Orebro Lan
    • Orebro, Orebro Lan, Sweden, 701 85
      • Orebro Universitetssjukhuset /ID# 228514
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Akademiska Sjukhuset /ID# 228515
• Turkey
  • Ankara, Turkey, 06200
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 234215
  • Istanbul, Turkey, 34010
    • Koc Universitesi Hastanesi Translasyonel Tıp Arastırma Merkezi /ID# 234214
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center /ID# 221790
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Duplicate_Dartmouth-Hitchcock Medical Center - 1 Medical Center Drive /ID# 224623
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute /ID# 222557
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital /ID# 221549
    • New York, New York, United States, 10065
      • Weill Cornell Medical College /ID# 227069
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research /ID# 222802
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104-5418
      • University of Oklahoma, Stephenson Cancer Center /ID# 224095
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University /ID# 221801
  • Texas
    • Dallas, Texas, United States, 75246-2003
      • Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004
  • Washington
    • Seattle, Washington, United States, 98108-1597
      • VA Puget Sound Health Care System /ID# 224208

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

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):

    1. >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib therapy;

    2. < 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.

    3. 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.

Exclusion Criteria:

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:

  • 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Segment A: ABBV-744 Dose Identification and Optimization; Participants 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.	Drug: ABBV-744; Tablet; Oral
Experimental: Segment A: ABBV-744 Monotherapy; Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.	Drug: ABBV-744; Tablet; Oral
Experimental: Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy; Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.	Drug: Ruxolitinib; Tablet; Oral; Drug: ABBV-744; Tablet; Oral
Experimental: Segment C: ABBV-744 + Navitoclax; Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.	Drug: Navitoclax; Tablet; Oral; Other Names: ABT-263; Drug: ABBV-744; Tablet; Oral
Experimental: Segment D: ABBV-744 + Ruxolitinib; Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.	Drug: Ruxolitinib; Tablet; Oral; Drug: ABBV-744; Tablet; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to Approximately 1 year from start of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up To Week 24
Maximum Observed Plasma Concentration (Cmax) of ABBV-744	Maximum observed plasma concentration (Cmax) of ABBV-744.	Up To Week 12
Time To Cmax (Tmax) Of ABBV-744	The amount of time taken to reach Cmax.	Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of ABBV-744	AUC of ABBV-744 will be calculated.	Up To Week 12
Half-Life (t1/2) Of ABBV-744	Half-life of ABBV-744 will be calculated.	Up To Week 12
Accumulation Ratio Of ABBV-744	Pharmacokinetic parameters will include accumulation ratio of ABBV-744.	Up To Week 12
Apparent Clearance (CL/F) Of ABBV-744	CL/F of ABBV-744 will be calculated.	Up To Week 12
Apparent Volume Of Distribution (Vd/F) Of ABBV-744	Vd/F of ABBV-744 will be calculated.	Up To Week 12
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).	Up to Week 24
Objective Response Rate (ORR)	ORR is defined as the sum of rates of partial remission (PR) or better.	Week 24
Maximum Observed Plasma Concentration (Cmax) Of Navitoclax	Maximum Observed Plasma Concentration (Cmax) Of Navitoclax.	Up To Week 12
Time To Cmax (Tmax) Of Navitoclax	The amount of time taken to reach Cmax.	Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of Navitoclax	AUC of Navitoclax will be calculated.	Up To Week 12
Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib	Maximum Observed Plasma Concentration (Cmax) Of Ruxolitinib.	Up To Week 12
Time To Cmax (Tmax) Of Ruxolitinib	The amount of time taken to reach Cmax.	Up To Week 12
Area Under The Concentration Versus Time Curve (AUC) Of Ruxolitinib	AUC of Ruxolitinib will be calculated.	Up To Week 12

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; Ruxolitinib; Myelofibrosis; MF; Navitoclax; ABT-263; ABBV-744
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Primary Myelofibrosis; Antineoplastic Agents; Navitoclax
• Other Study ID Numbers: M20-247; 2020-001225-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes