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

NCT04454658 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: M20-2472020-001225-32
• Study Type: interventional
• Target: 21
• Locations: 14 countries
• Sites: 43

Brief 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. 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.

Conditions

Myelofibrosis (MF)

Keywords

ABBV-744; Navitoclax; Ruxolitinib; ABT-263; Cancer; Myelofibrosis; MF

Outcome Measures

Primary Outcomes (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.

  Up to Approximately 1 year from start of study

Secondary Outcomes (16)

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

  Up To Week 24

• Maximum Observed Plasma Concentration (Cmax) of ABBV-744

  Up To Week 12

• Time To Cmax (Tmax) Of ABBV-744

  Up To Week 12

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

  Up To Week 12

• Half-Life (t1/2) Of ABBV-744

  Up To Week 12

Study Arms (5)

Segment A: ABBV-744 Dose Identification and Optimization

EXPERIMENTAL

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

Segment A: ABBV-744 Monotherapy

EXPERIMENTAL

Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.

Drug: ABBV-744

Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy

EXPERIMENTAL

Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.

Drug: ABBV-744; Drug: Ruxolitinib

Segment C: ABBV-744 + Navitoclax

EXPERIMENTAL

Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.

Drug: ABBV-744; Drug: Navitoclax

Segment D: ABBV-744 + Ruxolitinib

EXPERIMENTAL

Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.

Drug: ABBV-744; Drug: Ruxolitinib

Interventions

ABBV-744 DRUG

Tablet; Oral

Segment A: ABBV-744 Dose Identification and Optimization; Segment A: ABBV-744 Monotherapy; Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy; Segment C: ABBV-744 + Navitoclax; Segment D: ABBV-744 + Ruxolitinib

Navitoclax DRUG

Tablet; Oral

Also known as: ABT-263

Segment C: ABBV-744 + Navitoclax

Ruxolitinib DRUG

Tablet; Oral

Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy; Segment D: ABBV-744 + Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• \>= 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (43)

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

Sacramento, California, 95817, United States

Location

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

Lebanon, New Hampshire, 03756, United States

Location

Roswell Park Cancer Institute /ID# 222557

Buffalo, New York, 14263, United States

Location

The Mount Sinai Hospital /ID# 221549

New York, New York, 10029, United States

Location

Weill Cornell Medical College /ID# 227069

New York, New York, 10065, United States

Location

Gabrail Cancer Center Research /ID# 222802

Canton, Ohio, 44718, United States

Location

University of Oklahoma, Stephenson Cancer Center /ID# 224095

Oklahoma City, Oklahoma, 73104-5418, United States

Location

Oregon Health and Science University /ID# 221801

Portland, Oregon, 97239, United States

Location

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

Dallas, Texas, 75246-2003, United States

Location

VA Puget Sound Health Care System /ID# 224208

Seattle, Washington, 98108-1597, United States

Location

Hospital Universitario Austral /ID# 228909

Pilar, Buenos Aires, 1629, Argentina

Location

Hospital Italiano de Buenos Aires /ID# 226945

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

Location

Townsville University Hospital /ID# 225859

Douglas, Queensland, 4814, Australia

Location

Royal Hobart Hospital /ID# 241677

Hobart, Tasmania, 7000, Australia

Location

Royal Perth Hospital /ID# 241678

Perth, Western Australia, 6000, Australia

Location

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

Goiânia, Goiás, 74605-020, Brazil

Location

Hospital de Clinicas de Porto Alegre /ID# 226635

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Duplicate_Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640

São Paulo, São Paulo, 05652-900, Brazil

Location

Instituto Nacional de Cancer (INCA) /ID# 226637

Rio de Janeiro, 20231-050, Brazil

Location

Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641

São Paulo, 01323-001, Brazil

Location

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

São Paulo, 05403-000, Brazil

Location

SHAT Hematologic Diseases /ID# 226007

Sofia, 1797, Bulgaria

Location

UMHAT Sveta Marina /ID# 226681

Varna, 9010, Bulgaria

Location

Duplicate_Sociedad de Investigaciones Médicas Limitada /ID# 224175

Temuco, Región de la Araucanía, 4810469, Chile

Location

Icegclinic /Id# 231086

La Florida, Santiago Metropolitan, 8241479, Chile

Location

Fundacion Arturo Lopez Perez /ID# 225037

Providencia, Santiago Metropolitan, 7500921, Chile

Location

Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249

Gyöngyös, Heves County, 3200, Hungary

Location

Duplicate_Semmelweis Egyetem /ID# 224085

Budapest, 1085, Hungary

Location

Hadassah Medical Center-Hebrew University /ID# 243852

Jerusalem, Jerusalem, 91120, Israel

Location

The Chaim Sheba Medical Center /ID# 222151

Ramat Gan, Tel Aviv, 5265601, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 223548

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Duplicate_Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397

Milan, Milano, 20122, Italy

Location

Kyushu University Hospital /ID# 228035

Fukuoka, Fukuoka, 812-8582, Japan

Location

Duplicate_Hokkaido University Hospital /ID# 228038

Sapporo, Hokkaido, 060-8648, Japan

Location

Osaka Metropolitan University Hospital /ID# 225502

Osaka, Osaka, 545-8586, Japan

Location

University of Yamanashi Hospital /ID# 225503

Chuo-shi, Yamanashi, 409-3821, Japan

Location

Duplicate_Inje University Busan Paik Hospital /ID# 233707

Busan, Busan Gwang Yeogsi, 47392, South Korea

Location

Hospital Santa Creu i Sant Pau /ID# 238501

Barcelona, 08041, Spain

Location

Hospital General Universitario Gregorio Maranon /ID# 233279

Madrid, 28007, Spain

Location

Akademiska Sjukhuset /ID# 228515

Uppsala, Uppsala County, 751 85, Sweden

Location

Orebro Universitetssjukhuset /ID# 228514

Örebro, Örebro County, 701 85, Sweden

Location

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

Ankara, 06200, Turkey (Türkiye)

Location

Koc Universitesi Hastanesi Translasyonel Tıp Arastırma Merkezi /ID# 234214

Istanbul, 34010, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Neoplasms

Interventions

ABBV-744; navitoclax; ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 1, 2020
• Study Start: November 11, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (6); AR (2); BU (2); SE (2); TU (2); IL (3); CL (3); IT (1); JP (4); US (10); ES (2); KR (1); HU (2); AU (3)