To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

NCT ID: NCT04551053

Last Updated: 2025-10-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

177 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-26

Study Completion Date

2024-08-21

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Prospective participants must be on stable doses of ruxolitinib ranging from 5 mg BID to 25 mg BID and will have been on that dose for at least the last 8 weeks prior to Day 1. At least 3 months duration of prior ruxolitinib is required. Participants must meet Protocol-defined criteria for suboptimal response to ruxolitinib monotherapy. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10\^9/L vs 50 to \< 100 × 10\^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).

Once a participant has completed the week 24 assessments, the participant's treatment assignment will then be unblinded and if found to be placebo, the participant will have the opportunity to crossover to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Myelofibrosis Primary Myelofibrosis Post Essential Thrombocythemia Myelofibrosis Post Polycythemia Vera Myelofibrosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Triple blind

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Group A : ruxolitinib +parsaclisib

Participants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.

Group Type EXPERIMENTAL

parsaclisib

Intervention Type DRUG

parsaclisib will be administered QD orally

ruxolitinib

Intervention Type DRUG

ruxolitinib will be administered BID orally

Group B : ruxolitinib + placebo

Participants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.

Group Type PLACEBO_COMPARATOR

ruxolitinib

Intervention Type DRUG

ruxolitinib will be administered BID orally

placebo

Intervention Type DRUG

placebo will be administered QD orally

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

parsaclisib

parsaclisib will be administered QD orally

Intervention Type DRUG

ruxolitinib

ruxolitinib will be administered BID orally

Intervention Type DRUG

placebo

placebo will be administered QD orally

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

INCB050465 Jakafi Jakavi

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Diagnosis of PMF, PPV-MF, or PET-MF.
* DIPSS risk category of intermediate-1, intermediate-2, or high.
* Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1
* Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit.
* Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form.
* Participants with an ECOG performance status score of 0, 1, or 2.
* Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
* Life expectancy of at least 24 weeks.
* Willingness to avoid pregnancy or fathering children.

Exclusion Criteria

* Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
* Use of experimental drug therapy for MF or any other standard drug used for MF (whether for treatment of MF or another indication) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.
* Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
* Recent history of inadequate bone marrow reserve.
* Inadequate liver and renal function at screening.
* Active bacterial, fungal, parasitic, or viral infection that requires therapy.
* Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
* Known HIV infection.
* Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
* Active invasive malignancy over the previous 2 years.
* Splenic irradiation within 6 months before receiving the first dose of study drug.
* Concurrent use of any prohibited medications.
* Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
* Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
* Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
* Currently breastfeeding or pregnant.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* History of Grade 3 or 4 irAEs from prior immunotherapy.
* Receipt of any live vaccine within 30 days of the first dose of study drug
* Unwillingness to receive RBC transfusions to treat low hemoglobin levels.
* Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Albert Assad, M.D.

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

California Research Institute (Cri)

Los Angeles, California, United States

Site Status

Emad Ibrahim Md Inc

Redlands, California, United States

Site Status

Scripps Clinic

San Diego, California, United States

Site Status

Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, United States

Site Status

CCARE

Fresno, California, United States

Site Status

Coastal Integrated Cancer Care - Cicc

San Luis Obispo, California, United States

Site Status

Stamford Hospital - Medical Oncology Hematology

Stamford, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Augusta University - Medical College of Georgia

Augusta, Georgia, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

University of Kansas Hospital Authority

Westwood, Kansas, United States

Site Status

Tulane University

New Orleans, Louisiana, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Midamerica Cancer Care

Kansas City, Missouri, United States

Site Status

New Jersey Hematology Oncology Associates Llc

Brick, New Jersey, United States

Site Status

Morristown Medical Center - Atlantic Health System

Morristown, New Jersey, United States

Site Status

Westchester Medical Center Advanced Oncology

Hawthorne, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Advent Health Hendersonville Park Ridge Hospital Hendersonville

Clyde, North Carolina, United States

Site Status

Duke Cancer Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Columbus, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

Baptist Cancer Center

Memphis, Tennessee, United States

Site Status

Texas Oncology - Medical City Dallas

Dallas, Texas, United States

Site Status

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Renovatio Clinical

Houston, Texas, United States

Site Status

Kelsey Seybold Clinic

Houston, Texas, United States

Site Status

Providence Regional Medical Center Everett

Everett, Washington, United States

Site Status

Hanusch-Krankenhaus Wiener Gebietskrankenkasse

Vienna, , Austria

Site Status

A.Z. St.-Jan A.V.

Bruges, , Belgium

Site Status

Jessa Ziekenhuis

Hasselt, , Belgium

Site Status

AZ Delta

Roeselare, , Belgium

Site Status

Chu Ucl Namur University Hospital Mont-Godinne

Yvoir, , Belgium

Site Status

Peking University People'S Hospital (Pkuph) - Institute of Hematology

Beijing, , China

Site Status

Xuanwu Hospital Capital Medical University

Beijing, , China

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

Peking University Third Hospital

Beijing, , China

Site Status

The First Hospital of Jilin University

Changchun, , China

Site Status

The First Peoples Hospital of Changzhou

Changzhou, , China

Site Status

Fujian Medical University Union Hospital

Fuzhou, , China

Site Status

Nanfang Hospital

Guangzhou, , China

Site Status

The First Affiliated Hospital of Zhejiang University

Hangzhou, , China

Site Status

Harbin Institute of Hematology and Oncology

Harbin, , China

Site Status

University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)

Hefei, , China

Site Status

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, , China

Site Status

Jinan Central Hospital

Jinan, , China

Site Status

The Second Affiliated Hospital of Kunming Medical University

Kunming, , China

Site Status

The First Hospital of Lanzhou University

Lanzhou, , China

Site Status

Lanzhou University Second Hospital

Lanzhou, , China

Site Status

Jiangxi Provincial of People Hospital

Nanchang, , China

Site Status

The First Affiliated Hospital of Nanchang University

Nanchang, , China

Site Status

Jiangsu Province Hospital

Nanjing, , China

Site Status

The Affiliated Hospital of Qingdao University

Qingdao, , China

Site Status

The First Hospital of China Medical University

Shenyang, , China

Site Status

Shenzhen University Hospital

Shenzhen, , China

Site Status

Tianjin Medical University General Hospital

Tianjin, , China

Site Status

Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Pek

Tianjin, , China

Site Status

Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, , China

Site Status

Tongji Hospital Huazhong University of Science and Technology

Wuhan, , China

Site Status

The Second Affiliated Hospital of Xi an Jiaotong University

Xi'an, , China

Site Status

Yantai Yuhuangding Hospital

Yantai, , China

Site Status

Henan Provincial Peoples Hospital

Zhengzhou, , China

Site Status

Henan Cancer Hostipal

Zhengzhou, , China

Site Status

Helsinki University Central Hospital

Helsinki, , Finland

Site Status

Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon

La Tronche, , France

Site Status

Chu de Limoges

Limoges, , France

Site Status

CHU Limoges - Hopital Duputren

Limoges, , France

Site Status

Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu

Nantes, , France

Site Status

Chu Nimes

Nîmes, , France

Site Status

Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris)

Paris, , France

Site Status

Hospital Saint Antoine

Paris, , France

Site Status

Hospices Civils de Lyon Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Institut Universitaire Du Cancer de Toulouse Oncopole

Toulouse, , France

Site Status

Chu Vandoeuvre-Les-Nancy Hopital Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Universitatsklinikum Bonn Aoer

Bonn, , Germany

Site Status

Universitaetsmedizin Greifswald

Greifswald, , Germany

Site Status

Universitatsklinikum Halle (Saale)

Halle, , Germany

Site Status

Universitaetsmedizin Rostock

Rostock, , Germany

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Markhot Ferenc Korhaz

Eger, , Hungary

Site Status

Petz Aladar County Teaching Hospital

Győr, , Hungary

Site Status

Samson Assuta Ashdod University Hospital

Ashdod, , Israel

Site Status

Rambam Health Care Campus

Haifa, , Israel

Site Status

Hadassah Hebrew University Medical Center Ein Karem Hadassah

Jerusalem, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Assuta Ramat Hahayal

Tel Aviv, , Israel

Site Status

Azienda Ospedaliera San Giuseppe Moscati

Avellino, , Italy

Site Status

Aou Policlinico Consorziale Di Bari

Bari, , Italy

Site Status

Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or

Bologna, , Italy

Site Status

Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi

Catania, , Italy

Site Status

University of Florence

Florence, , Italy

Site Status

Irccs Azienda Ospedaliera Universitaria San Martino

Genova, , Italy

Site Status

Fondazione Irccs Ca Granda Ospedale Maggiore

Milan, , Italy

Site Status

Universita Di Napoli Federico Ii

Napoli, , Italy

Site Status

Azienda Ospedaliero Universitaria Maggiore Della Carita Di Novara

Novara, , Italy

Site Status

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello

Palermo, , Italy

Site Status

Ospedale S.Maria Della Misericordia

Perugia, , Italy

Site Status

Ospedale S.Maria Della Misericordia

Perugia, , Italy

Site Status

Presidio Ospedaliero Pescara

Pescara, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Site Status

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Reggio Calabria, , Italy

Site Status

Univ. Di Roma Facolta Di Armacia E Medicina

Roma, , Italy

Site Status

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Roma, , Italy

Site Status

Ospedale Sant. Eugenio

Roma, , Italy

Site Status

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Rome, , Italy

Site Status

Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte

Siena, , Italy

Site Status

Azienda Ospedaliera San Giuseppe Moscati

Taranto, , Italy

Site Status

Azienda Sanitaria Universitaria Friuli Centrale Asu Fc

Udine, , Italy

Site Status

A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi

Varese, , Italy

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Japanese Red Cross Society Himeji Hospital

Himeji-shi, , Japan

Site Status

Kansai Medical University Hospital

Hirakata, , Japan

Site Status

Tokai University Hospital

Isehara, , Japan

Site Status

Juntendo University Hospital

Izunokuni, , Japan

Site Status

Kagoshima University Hospital

Kagoshima, , Japan

Site Status

Hospital of the University of Occupation and Environmental Health

Kitakyushu-shi, , Japan

Site Status

Kobe City Medical Center General Hospital

Kobe, , Japan

Site Status

Kumamoto Shinto General Hospital

Kumamoto, , Japan

Site Status

University of Miyazaki Hospital

Miyazaki, , Japan

Site Status

Japanese Red Cross Nagoya Daini Hospital

Nagoya, , Japan

Site Status

Osaka Metropolitan University Hospital

Osaka, , Japan

Site Status

Ogaki Municipal Hospital

Ōgaki, , Japan

Site Status

Dokkyo Medical University Saitama Medical Center

Saitama, , Japan

Site Status

Hokuyukai Sapporo Hokuyu Hospital

Sapporo, , Japan

Site Status

Juntendo University Hospital

Tokyo, , Japan

Site Status

Nippon Medical School Hospital

Tokyo, , Japan

Site Status

University of Yamanashi Hospital

Yamanashi, , Japan

Site Status

Haukeland University Hospital

Bergen, , Norway

Site Status

Akershus University Hospital

Lorenskog, , Norway

Site Status

Pratia Hematologia Katowice

Katowice, , Poland

Site Status

Pratia Hematologia Katowice

Katowice, , Poland

Site Status

Samodzielny Publiczny Zoz Szpital Uniwersytecki W Krakowie

Krakow, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny Nr 1

Lublin, , Poland

Site Status

Institute of Hematology and Transfusion Medicine

Warsaw, , Poland

Site Status

Spitalul Clinic Coltea - Clinica Hematologie

Bucharest, , Romania

Site Status

Spitalul Clinic Judetean de Urgenta Targu Mures

Târgu Gânguleşti, , Romania

Site Status

Pusan National University Yangsan Hospital

Busan, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea Seoul St. Mary?S Hospital

Seoul, , South Korea

Site Status

Hospital General Unviersitario de Alicante

Alicante, , Spain

Site Status

Ico Hospital Germans Trias I Pujol

Badalona, , Spain

Site Status

Hospital Del Mar

Barcelona, , Spain

Site Status

Hospital General Universitario Vall D Hebron

Barcelona, , Spain

Site Status

Institut Catala Doncologia Ico - Hospital Duran I Reynals Location

Barcelona, , Spain

Site Status

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Fundacion Jimenez Diaz University Hospital

Madrid, , Spain

Site Status

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Site Status

Hospital Universitario Virgen de La Arrixaca

Murcia, , Spain

Site Status

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Hospital Universitari I Politecnic La Fe

Valencia, , Spain

Site Status

Hospital Universitario Doctor Peset

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University (Ncku) Hospital

Tainan City, , Taiwan

Site Status

Baskent University Adana Hospital

Adana, , Turkey (Türkiye)

Site Status

Gazi University Hospital Gazi University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

Baskent University Istanbul Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Ege University Hospital

Izmir, , Turkey (Türkiye)

Site Status

Ondokuz Mayis University Medicine Faculty

Samsun, , Turkey (Türkiye)

Site Status

Grampian Health Board

Aberdeen, , United Kingdom

Site Status

United Lincolnshire Hospitals

Boston, , United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, , United Kingdom

Site Status

University College London Hospitals Nhs Foundation Trust

London, , United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Austria Belgium China Finland France Germany Hungary Israel Italy Japan Norway Poland Romania South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2020-003415-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 50465-304/LIMBER-304

Identifier Type: -

Identifier Source: org_study_id

NCT04816565

Identifier Type: -

Identifier Source: nct_alias

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Multiple Ascending Dose of BMS-911543
NCT01236352 TERMINATED PHASE1/PHASE2