To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)

NCT ID: NCT04551066

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 252 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-24
• Study Completion Date: 2024-11-25

Brief Summary

The purpose of the study is to compare the efficacy of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.

Detailed Description

This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high. Prospective participants must have not received prior MF therapy with a JAK inhibitor or a PI3K inhibitor. 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 all enrolled participants completed the week 24 assessments the study will be unblinded and and participants randomized to placebo will have the opportunity to cross over to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

Conditions

Myelofibrosis; Primary Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis; Post Polycythemia Vera Myelofibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group A : parsaclisib + ruxolitinib

Participants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.

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 : placebo + ruxolitinib

Participants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.

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

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

INCB050465; Jakafi; Jakavi

Eligibility Criteria

Inclusion Criteria

• Diagnosis of PMF, PPV-MF, or PET-MF.
• DIPSS risk category of intermediate-1, intermediate-2, or high.
• 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 use of any JAK inhibitor.
• 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 (eg, danazol, hydroxyurea) used for MF within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 1.
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Assad, M.D

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Alaska Oncology and Hematology

Anchorage, Alaska, United States

Mayo Clinic Rochester

Phoenix, Arizona, United States

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

Berkeley, California, United States

CCARE

Fresno, California, United States

California Research Institute (Cri)

Los Angeles, California, United States

UCLA School of Medicine

Los Angeles, California, United States

Scripps Clinic

San Diego, California, United States

Coastal Integrated Cancer Care-Cicc

San Luis Obispo, California, United States

Stamford Hospital-Medical Oncology Hematology

Stamford, Connecticut, United States

Georgetown University

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

Emory University

Atlanta, Georgia, United States

University of Kansas Hospital Authority

Westwood, Kansas, United States

University of Kentucky-Markey Cancer Center

Lexington, Kentucky, United States

Tulane University

New Orleans, Louisiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Midamerica Cancer Care

Kansas City, Missouri, United States

New Jersey Hematology Oncology Associates Llc

Brick, New Jersey, United States

Morristown Medical Center-Atlantic Health System

Morristown, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Westchester Medical Center Advanced Oncology and Infusion Center

Hawthorne, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke Cancer Center

Durham, North Carolina, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Kaiser Permanente-Northwest

Portland, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States

Kelsey Seybold Clinic

Houston, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Renovatio Clinical

Spring, Texas, United States

Providence Regional Medical Center Everett

Everett, Washington, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Ordensklinikum Linz Gmbh Elisabethinen

Linz, , Austria

Universitaetsklinikum St. Poelten

Saint P�LTEN, , Austria

Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse

Vienna, , Austria

Hanusch-Krankenhaus Wiener Gebietskrankenkasse

Vienna, , Austria

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

Bruges, , Belgium

Cliniques Universitaires Ucl Saint-Luc

Brussels, , Belgium

Grand Hospital de Charleroi

Charleroi, , Belgium

Jessa Ziekenhuis

Hasselt, , Belgium

AZ DELTA

Roeselare, , Belgium

Affiliated Hospital of Hebei University

Baoding, , China

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

Beijing, , China

Peking University Third Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

Xiangya Hospital Central South University

Changsha, , China

Fujian Medical University Union Hospital

Fuzhou, , China

Guangdong Provincial of People Hospital

Guangzhou, , China

Nanfang Hospital

Guangzhou, , China

The First Affiliated Hospital of Zhejiang University

Hangzhou, , China

Harbin Institute of Hematology and Oncology

Harbin, , China

Anhui Provincial Hospital

Hefei, , China

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, , China

Jinan Central Hospital

Jinan, , China

The First Hospital of Lanzhou University

Lanzhou, , China

Lanzhou University Second Hospital

Lanzhou, , China

Jiangxi Provincial of People Hospital

Nanchang, , China

The First Affiliated Hospital of Nanchang University

Nanchang, , China

Jiangsu Province Hospital

Nanjing, , China

Zhongshan Hospital Fudan University

Shanghai, , China

Shenzhen University Hospital

Shenzhen, , China

The Second Hospital of Hebei Medical University

Shijiazhuang, , China

Tianjin Medical University General Hospital

Tianjin, , China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, , China

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

Wuhan, , China

Yantai Yuhuangding Hospital

Yantai, , China

Henan Provincial Peoples Hospital

Zhengzhou, , China

Aalborg University Hospital

Aalborg, , Denmark

Odense University Hospital

Odense, , Denmark

Helsinki University Central Hospital

Helsinki, , Finland

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

La Tronche, , France

Centre Hospitalier de Versailles - Hopital Andre Mignot

LE Chesnay-rocquencourt, , France

Chu Limoges - Hopital Dupuytren

Limoges, , France

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

Nantes, , France

Chu Nimes

Nîmes, , France

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

Paris, , France

Hospices Civils de Lyon Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Hospital de La Miletrie

Poitiers, , France

Chu de Rennes - Hospital Pontchaillou

Rennes, , France

Centre Hospitalier de Roubaix

Roubaix, , France

Universitatsklinikum Halle (Saale)

Halle, , Germany

Klinikum Kassel Gmbh

Kassel, , Germany

Universitatsklinikum Magdeburg A.O.R.

Magdeburg, , Germany

Universitaetsmedizin Rostock

Rostock, , Germany

Shamir Medical Center Formerly Assaf Harofeh Medical Center

BEER Yaaqov, , Israel

Rambam Health Care Campus

Haifa, , Israel

Hadassah Hebrew University Medical Center Ein Karem Hadassah

Jerusalem, , Israel

Davidoff Cancer Center Rabin Medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Assuta Ramat Hahayal

Tel Aviv, , Israel

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

Bologna, , Italy

Azienda Policlinico Vittorio Emanuele

Catania, , Italy

Universita Degli Studi Di Genova - Facolta Di Medicina E Chirurgia

Genova, , Italy

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori

Meldola, , Italy

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele

Milan, , Italy

Fondazione Irccs Ca Granda Ospedale Maggiore

Milan, , Italy

Universita Di Napoli Federico Ii

Napoli, , Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello

Palermo, , Italy

Aormn Hospital Hematology and Bmt Center

Pesaro, , Italy

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Reggio Calabria, , Italy

Universita Di Roma Tor Vergata

Roma, , Italy

Universita Di Roma

Roma, , Italy

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Roma, , Italy

Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore

Rome, , Italy

Aou San Giovanni Di Dio E Ruggi D'Aragona

Salerno, , Italy

Azienda Ospedaliera San Giuseppe Moscati

Taranto, , Italy

Azienda Sanitaria Universitaria Friuli Centrale Asu Fc

Udine, , Italy

A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi

Varese, , Italy

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)

Verona, , Italy

Chiba Cancer Center

Chiba, , Japan

University of Yamanashi Hospital

Chūō, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Japanese Red Cross Society Himeji Hospital

Himeji-shi, , Japan

Kansai Medical University Hospital

Hirakata, , Japan

Tokai University Hospital

Isehara, , Japan

Kagoshima University Hospital

Kagoshima, , Japan

Hospital of the University of Occupation and Environmental Health

Kitakyushu-shi, , Japan

Kobe City Medical Center General Hospital

Kobe, , Japan

Kumamoto Shinto General Hospital

Kumamoto, , Japan

University of Miyazaki Hospital

Miyazaki, , Japan

Japanese Red Cross Nagoya Daini Hospital

Nagoya, , Japan

Osaka Metropolitan University Hospital

Osaka, , Japan

Ogaki Municipal Hospital

Ōgaki, , Japan

Dokkyo Medical University Saitama Medical Center

Saitama, , Japan

Hokuyukai Sapporo Hokuyu Hospital

Sapporo, , Japan

Tohoku University Hospital

Sendai, , Japan

Juntendo University Hospital

Tokyo, , Japan

Nippon Medical School Hospital

Tokyo, , Japan

Mie University Hospital

Tsu, , Japan

Yokohama Municipal Citizens Hospital

Yokohama, , Japan

Haukeland University Hospital

Bergen, , Norway

Akershus University Hospital

L�RENSKOG, , Norway

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Samodzielny Publiczny Szpital Kliniczny Im. Andrzeja Mielckiego

Katowice, , Poland

Pratia Hematologia Katowice

Katowice, , Poland

Sp Zoz Szpital Uniwersytecki

Krakow, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1

Lublin, , Poland

Institute of Hematology and Transfusion Medicine

Warsaw, , Poland

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

THE CATHOLIC UNIVERSITY OF KOREA SEOUL ST. MARY�S HOSPITAL

Seoul, , South Korea

Wonju Severance Christian Hospital

Wŏnju, , South Korea

Hospital General Unviersitario de Alicante

Alicante, , Spain

Ico Hospital Germans Trias I Pujol

Badalona, , Spain

Hospital Del Mar

Barcelona, , Spain

Hospital General Universitario Vall D Hebron

Barcelona, , Spain

Ico-Hospital Duran I Reynals

Barcelona, , Spain

Institut Catala Doncologia Ico - Hospital Duran I Reynals Location

Barcelona, , Spain

Ico Hospital Germans Trias I Pujol

Barcelona, , Spain

Hospital de Basurto

Bilbao, , Spain

Hospital Universitario Virgen de La Arrixaca

El Palmar, , Spain

Hospital Universitario Virgen de Las Nieves

Granada, , Spain

Hospital Universitario Insular de Gran Canaria

Las Palmas de Gran Canaria, , Spain

Fundacian Jimnez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitari I Politecnic La Fe

Valencia, , Spain

Hospital Universitario Doctor Peset

Valencia, , Spain

Baskent University Adana Hospital

Adana, , Turkey (Türkiye)

Gazi University Hospital Gazi University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi

Istanbul, , Turkey (Türkiye)

Baskent University Istanbul Hospital

Istanbul, , Turkey (Türkiye)

Ege University Hospital

Izmir, , Turkey (Türkiye)

Dokuz Eylul University

Izmir, , Turkey (Türkiye)

Ondokuz Mayis University Medicine Faculty

Samsun, , Turkey (Türkiye)

United Lincolnshire Hospitals

Boston, , United Kingdom

Gloucestershire Royal Hospital

Gloucester, , United Kingdom

Barts Health Nhs Trust - St Bartholomews Hospital

London, , United Kingdom

University College London Hospitals Nhs Foundation Trust

London, , United Kingdom

Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital

Sheffield, , United Kingdom

University Hospital of North Midlands Nhs Trust

Stoke-on-Trent, , United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.incyteclinicaltrials.com/limber/

Related Info

Other Identifiers

2020-003130-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 50465-313/LIMBER-313

Identifier Type: -

Identifier Source: org_study_id

NCT04816578

Identifier Type: -

Identifier Source: nct_alias