Ireland
--:--IST
Latest
Clinical Trials in Italy / NCT04454658
Active, not recruiting Phase 1

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 · tracked via the Priya Life Science Italy tracker
Sponsor
Phase
Phase 1
Started
2020-11-11
Last updated
2025-07-16

Condition(s) studied

Myelofibrosis (MF)

Investigational drug(s) / intervention(s)

ABBV-744Navitoclax →Ruxolitinib →

ABBV-744: Tablet; Oral

Navitoclax: Tablet; Oral

Ruxolitinib: Tablet; Oral

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.

Primary outcome measure(s)

Trial sites (43)

FacilityCityRegionStatus
University of California, Davis Comprehensive Cancer Center /ID# 221790 Sacramento California
Duplicate_Dartmouth-Hitchcock Medical Center - 1 Medical Center Drive /ID# 224623 Lebanon New Hampshire
Roswell Park Cancer Institute /ID# 222557 Buffalo New York
The Mount Sinai Hospital /ID# 221549 New York New York
Weill Cornell Medical College /ID# 227069 New York New York
Gabrail Cancer Center Research /ID# 222802 Canton Ohio
University of Oklahoma, Stephenson Cancer Center /ID# 224095 Oklahoma City Oklahoma
Oregon Health and Science University /ID# 221801 Portland Oregon
Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004 Dallas Texas
VA Puget Sound Health Care System /ID# 224208 Seattle Washington
Hospital Universitario Austral /ID# 228909 Pilar Buenos Aires
Hospital Italiano de Buenos Aires /ID# 226945 Ciudad Autonoma Buenos Aires Buenos Aires F.D.
Townsville University Hospital /ID# 225859 Douglas Queensland
Royal Hobart Hospital /ID# 241677 Hobart Tasmania
Royal Perth Hospital /ID# 241678 Perth Western Australia
Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636 Goiânia Goiás
Hospital de Clinicas de Porto Alegre /ID# 226635 Porto Alegre Rio Grande do Sul
Duplicate_Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640 São Paulo São Paulo
Instituto Nacional de Cancer (INCA) /ID# 226637 Rio de Janeiro Brazil
Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641 São Paulo Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao /ID# 226639 São Paulo Brazil
SHAT Hematologic Diseases /ID# 226007 Sofia Bulgaria
UMHAT Sveta Marina /ID# 226681 Varna Bulgaria
Duplicate_Sociedad de Investigaciones Médicas Limitada /ID# 224175 Temuco Araucania
Icegclinic /Id# 231086 La Florida Santiago Metropolitan
Fundacion Arturo Lopez Perez /ID# 225037 Providencia Santiago Metropolitan
Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249 Gyöngyös Heves County
Duplicate_Semmelweis Egyetem /ID# 224085 Budapest Hungary
Hadassah Medical Center-Hebrew University /ID# 243852 Jerusalem Jerusalem
The Chaim Sheba Medical Center /ID# 222151 Ramat Gan Tel Aviv
Tel Aviv Sourasky Medical Center /ID# 223548 Tel Aviv Tel Aviv
Duplicate_Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397 Milan Milano
Kyushu University Hospital /ID# 228035 Fukuoka Fukuoka
Duplicate_Hokkaido University Hospital /ID# 228038 Sapporo Hokkaido
Osaka Metropolitan University Hospital /ID# 225502 Osaka Osaka
University of Yamanashi Hospital /ID# 225503 Chuo-shi Yamanashi
Duplicate_Inje University Busan Paik Hospital /ID# 233707 Busan Busan Gwang Yeogsi
Hospital Santa Creu i Sant Pau /ID# 238501 Barcelona Spain
Hospital General Universitario Gregorio Maranon /ID# 233279 Madrid Spain
Akademiska Sjukhuset /ID# 228515 Uppsala Uppsala County

+ 3 more sites — see the full list on the official registry below.

On this site

📄 Jakafi (ruxolitinib) drug profile →

More AbbVie trials in Italy

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04454658 on ClinicalTrials.gov ↗ ← All trials in Italy