MyelofibrosisPhase 3NCT04551053
To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)
A Phase 3 study testing parsaclisib and ruxolitinib in people with Myelofibrosis and Primary Myelofibrosis, run by Incyte Corporation at 177 sites in 19 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis, Primary Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis
- What is being tested?
- parsaclisib and ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 177 participants
- Where
- 177 sitesin 19 countries
- Study dates
- 26 May 2021to 21 Aug 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
177 sites in 19 countries.
177 sites in 19 countries
United States35 sites
Emory University
Atlanta, Georgia, 30322
Augusta University - Medical College of Georgia
Augusta, Georgia, 30912
Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center
Berkeley, California, 94704
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
New Jersey Hematology Oncology Associates Llc
Brick, New Jersey, 08724
Cleveland Clinic
Cleveland, Ohio, 44195
Advent Health Hendersonville Park Ridge Hospital Hendersonville
Clyde, North Carolina, 28721
Oregon Health & Science University
Columbus, Ohio, 43210
Texas Oncology - Medical City Dallas
Dallas, Texas, 75230
Texas Oncology - Baylor Sammons Cancer Center
Dallas, Texas, 75246-2092
University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8565
Duke Cancer Center
Durham, North Carolina, 27710
Providence Regional Medical Center Everett
Everett, Washington, 98201
CCARE
Fresno, California, 93720
Westchester Medical Center Advanced Oncology
Hawthorne, New York, 10532
Renovatio Clinical
Houston, Texas, 77005
Kelsey Seybold Clinic
Houston, Texas, 77025
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Midamerica Cancer Care
Kansas City, Missouri, 64114
California Research Institute (Cri)
Los Angeles, California, 90027-6005
Baptist Cancer Center
Memphis, Tennessee, 38120
Morristown Medical Center - Atlantic Health System
Morristown, New Jersey, 07960
Tulane University
New Orleans, Louisiana, 70112
Mount Sinai School of Medicine
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Oregon Health & Science University
Portland, Oregon, 97239
Emad Ibrahim Md Inc
Redlands, California, 92373
Scripps Clinic
San Diego, California, 92103
Coastal Integrated Cancer Care - Cicc
San Luis Obispo, California, 93401
Stamford Hospital - Medical Oncology Hematology
Stamford, Connecticut, 06904
Montefiore Medical Center
The Bronx, New York, 10467
Georgetown University
Washington D.C., District of Columbia, 20057
University of Kansas Hospital Authority
Westwood, Kansas, 66205
China30 sites
Peking University People'S Hospital (Pkuph) - Institute of Hematology
Beijing, 100044
Xuanwu Hospital Capital Medical University
Beijing, 100053
Peking University Third Hospital
Beijing, 100091
Peking University Third Hospital
Beijing, 100191
The First Hospital of Jilin University
Changchun, 130021
The First Peoples Hospital of Changzhou
Changzhou, 213003
Fujian Medical University Union Hospital
Fuzhou, 350001
Nanfang Hospital
Guangzhou, 510515
The First Affiliated Hospital of Zhejiang University
Hangzhou, 310003
Harbin Institute of Hematology and Oncology
Harbin, 150010
University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)
Hefei, 230022
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, 10050
Jinan Central Hospital
Jinan, 250013
The Second Affiliated Hospital of Kunming Medical University
Kunming, 650101
The First Hospital of Lanzhou University
Lanzhou, 730000
Lanzhou University Second Hospital
Lanzhou, 730030
Jiangxi Provincial of People Hospital
Nanchang, 330000
The First Affiliated Hospital of Nanchang University
Nanchang, 330006
Jiangsu Province Hospital
Nanjing, 210029
The Affiliated Hospital of Qingdao University
Qingdao, 266003
The First Hospital of China Medical University
Shenyang, 110001
Shenzhen University Hospital
Shenzhen, 518055
Tianjin Medical University General Hospital
Tianjin, 300052
Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Pek
Tianjin, 510080
Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, 430022
Tongji Hospital Huazhong University of Science and Technology
Wuhan, 430030
The Second Affiliated Hospital of Xi an Jiaotong University
Xi'an, 710004
Yantai Yuhuangding Hospital
Yantai, 264000
Henan Provincial Peoples Hospital
Zhengzhou, 450003
Henan Cancer Hostipal
Zhengzhou, 450008
Italy23 sites
Azienda Ospedaliera San Giuseppe Moscati
Avellino, 83100
Aou Policlinico Consorziale Di Bari
Bari, 70124
Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or
Bologna, 40138
Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
Catania, 11111
University of Florence
Florence, 50134
Irccs Azienda Ospedaliera Universitaria San Martino
Genova, 16132
Fondazione Irccs Ca Granda Ospedale Maggiore
Milan, 20122
Universita Di Napoli Federico Ii
Naples, 80131
Azienda Ospedaliero Universitaria Maggiore Della Carita Di Novara
Novara, 28100
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
Palermo, 90146
Ospedale S.Maria Della Misericordia
Perugia, 06156
Ospedale S.Maria Della Misericordia
Perugia, 6156
Presidio Ospedaliero Pescara
Pescara, 65124
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
Reggio Calabria, 89133
Univ. Di Roma Facolta Di Armacia E Medicina
Roma, 00161
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
Roma, 00168
Ospedale Sant. Eugenio
Roma, 144
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
Rome, 00168
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
Siena, 53100
Azienda Ospedaliera San Giuseppe Moscati
Taranto, 74123
Azienda Sanitaria Universitaria Friuli Centrale Asu Fc
Udine, 33100
A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi
Varese, 21100
Japan18 sites
Kyushu University Hospital
Fukuoka, 812-8582
Japanese Red Cross Society Himeji Hospital
Himeji-shi, 670-8540
Kansai Medical University Hospital
Hirakata, 573-1191
Tokai University Hospital
Isehara, 2591193
Juntendo University Hospital
Izunokuni, 410-2211
Kagoshima University Hospital
Kagoshima, 890-8520
Hospital of the University of Occupation and Environmental Health
Kitakyushu-shi, 807-8556
Kobe City Medical Center General Hospital
Kobe, 650-0047
Kumamoto Shinto General Hospital
Kumamoto, 862-8655
University of Miyazaki Hospital
Miyazaki, 889-1692
Japanese Red Cross Nagoya Daini Hospital
Nagoya, 453-8511
Ogaki Municipal Hospital
Ōgaki, 5038502
Osaka Metropolitan University Hospital
Osaka, 545-8585
Dokkyo Medical University Saitama Medical Center
Saitama, 343-8555
Hokuyukai Sapporo Hokuyu Hospital
Sapporo, 003-0006
Juntendo University Hospital
Tokyo, 113-8431
Nippon Medical School Hospital
Tokyo, 113-8603
University of Yamanashi Hospital
Yamanashi, 409-3898
Spain15 sites
Hospital General Unviersitario de Alicante
Alicante, 03010
Ico Hospital Germans Trias I Pujol
Badalona, 08916
Hospital Del Mar
Barcelona, 08003
Hospital General Universitario Vall D Hebron
Barcelona, 08035
Institut Catala Doncologia Ico - Hospital Duran I Reynals Location
Barcelona, 08908
Hospital Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria, 35010
Hospital Universitario 12 de Octubre
Madrid, 24041
Fundacion Jimenez Diaz University Hospital
Madrid, 28040
Hospital General Universitario Morales Meseguer
Murcia, 30008
Hospital Universitario Virgen de La Arrixaca
Murcia, 30120
Hospital Clinico Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Virgen Del Rocio
Seville, 41013
Hospital Universitari I Politecnic La Fe
Valencia, 46000
Hospital Universitario Doctor Peset
Valencia, 46017
Hospital Universitario Miguel Servet
Zaragoza, 50009
France10 sites
Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon
La Tronche, 38700
Chu de Limoges
Limoges, 87042
CHU Limoges - Hopital Duputren
Limoges, 87042
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
Nantes, 44093
Chu Nimes
Nîmes, 30900
Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris)
Paris, 75010
Hospital Saint Antoine
Paris, 75012
Hospices Civils de Lyon Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Institut Universitaire Du Cancer de Toulouse Oncopole
Toulouse, 31059
Chu Vandoeuvre-Les-Nancy Hopital Brabois
Vandœuvre-lès-Nancy, 54500
Israel6 sites
Samson Assuta Ashdod University Hospital
Ashdod, 7747629
Rambam Health Care Campus
Haifa, 31999
Hadassah Hebrew University Medical Center Ein Karem Hadassah
Jerusalem, 91120
Kaplan Medical Center
Rehovot, 76100
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Assuta Ramat Hahayal
Tel Aviv, 69710
Turkey (Türkiye)6 sites
Baskent University Adana Hospital
Adana, 01250
Gazi University Hospital Gazi University Faculty of Medicine
Ankara, 06500
Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi
Istanbul, 34214
Baskent University Istanbul Hospital
Istanbul, 34662
Ege University Hospital
Izmir, 35040
Ondokuz Mayis University Medicine Faculty
Samsun, 55200
Poland5 sites
Pratia Hematologia Katowice
Katowice, 40-040
Pratia Hematologia Katowice
Katowice, 41-081
Samodzielny Publiczny Zoz Szpital Uniwersytecki W Krakowie
Krakow, 31-501
Samodzielny Publiczny Szpital Kliniczny Nr 1
Lublin, 20-081
Institute of Hematology and Transfusion Medicine
Warsaw, 02-776
United Kingdom5 sites
Grampian Health Board
Aberdeen, AB15 6RE
United Lincolnshire Hospitals
Boston, PE21 9QS
Gloucestershire Royal Hospital
Gloucester, GL1 3NN
University College London Hospitals Nhs Foundation Trust
London, NW1 2BU
James Cook University Hospital
Middlesbrough, TS4 3BW
Belgium4 sites
A.Z. St.-Jan A.V.
Bruges, 08000
Jessa Ziekenhuis
Hasselt, 3500
AZ Delta
Roeselare, 8800
Chu Ucl Namur University Hospital Mont-Godinne
Yvoir, 05530
Germany4 sites
Universitatsklinikum Bonn Aoer
Bonn, 53127
Universitaetsmedizin Greifswald
Greifswald, 17475
Universitatsklinikum Halle (Saale)
Halle, 06120
Universitaetsmedizin Rostock
Rostock, 18057
South Korea4 sites
Pusan National University Yangsan Hospital
Busan, 49241
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
The Catholic University of Korea Seoul St. Mary?S Hospital
Seoul, 06591
Hungary3 sites
Semmelweis Egyetem
Budapest, 01088
Markhot Ferenc Korhaz
Eger, 03300
Petz Aladar County Teaching Hospital
Győr, 09024
Taiwan3 sites
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
China Medical University Hospital
Taichung, 00404
National Cheng Kung University (Ncku) Hospital
Tainan, 00704
Norway2 sites
Haukeland University Hospital
Bergen, 05021
Akershus University Hospital
Lorenskog, 01478
Romania2 sites
Spitalul Clinic Coltea - Clinica Hematologie
Bucharest, 30171
Spitalul Clinic Judetean de Urgenta Targu Mures
Târgu Gânguleşti, 540139
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib
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.
Read the detailed description
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
- Myelofibrosis, Primary Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia Vera Myelofibrosis
- Being tested
- parsaclisib, ruxolitinib, placebo
- Keywords
- INCB050465, ruxolitinib, parsaclisib, LIMBER, LIMBER-304, MF, MPN, Myeloproliferative Neoplasm, Myelofibrosis, Myoproliferative Neoplasms
- Medical subject headings
- Primary Myelofibrosis, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
parsaclisibDrug
Also called INCB050465
parsaclisib will be administered QD orally
ruxolitinibDrug
Also called Jakafi, Jakavi
ruxolitinib will be administered BID orally
placeboDrug
placebo will be administered QD orally
| Study group | Role | What they receive |
|---|---|---|
| Group A : ruxolitinib +parsaclisib | Experimental | 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. Receives: Drug: parsaclisib; Drug: ruxolitinib |
| Group B : ruxolitinib + placebo | Placebo comparator | 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. Receives: Drug: ruxolitinib; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)
Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available.
Measured: Baseline; Week 24
Secondary outcomes (8)
Percentage of Participants Who Have a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary
Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total score was marked as missing if there were ≥4 out of the 7 daily TSSs missing.
Measured: Baseline; Week 24
Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary
Symptoms of myelofibrosis were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total score was marked as missing if there were ≥4 out of the 7 daily TSSs missing. Change from Baseline was calculated as the Week 24 value minus the Baseline value.
Measured: Baseline; Week 24
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary
Symptoms were assessed using the MFSAF v4.0 diary. The MFSAF v4.0 is composed of 7 individual symptom scores (fatigue, night sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone pain), each collected daily using a 0- (no symptoms) to 10-point (worst imaginable symptoms) scale. The daily TSS (0 to 70) is the sum of the 7 individual symptom scores collected in a day. A higher TSS corresponds to more severe symptoms. The TSS was marked as missing if there were any missing individual scores. Observations with missing dates were excluded from the analysis. The Baseline/Week 24 total score was defined as the average of the daily total scores from the last 7 days before the first dose of parsaclisib, placebo, or ruxolitinib/the Week 24 visit. The Baseline/Week 24 total scores was marked as missing if there were ≥4 out of the 7 daily TSSs missing. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method with log-log transformation.
Measured: Baseline; up to Week 24
Overall Survival
Overall survival was defined as the interval between the randomization date and the date of death due to any cause.
Measured: up to 917 days
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
Measured: up to 917 days
Number of Participants With Any Grade 3 or Higher TEAE
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is defined as an AE reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated; limiting instrumental activities of daily living (ADL). Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: life-threatening urgent intervention indicated. Grade 5: death related to AE.
Measured: up to 917 days
Time to the First ≥25% Reduction in Spleen Volume
The time to the first ≥25% reduction in spleen volume is defined as the time from randomization to the first time participants had ≥25% reduction in spleen volume. Participants with a Baseline and post-Baseline MRI or CT scan who did not have ≥25% reduction in spleen volume at the time of analysis were censored at the time of the last MRI or CT scan. If the participants had no Baseline or post-Baseline MRI or CT scan, they were censored at the date of randomization.
Measured: up to 898 days
Duration of Maintenance of a ≥25% Reduction in Spleen Volume
The duration of ≥25% reduction from Baseline in spleen volume was defined as the interval between the first spleen volume measurement that was a ≥25% reduction from Baseline and the date of the first measurement that was no longer a ≥25% reduction from Baseline. If the end date was not observed before the database cutoff, the duration was censored at the last assessment.
Measured: up to 898 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start26 May 2021
- Primary completion16 Aug 2023
- Study completion21 Aug 2024
Why it stopped: The study was terminated due to futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Incyte CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 177 participants (actual)
Sponsor and investigators
- Lead sponsor
- Incyte Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Albert Assad, M.D., Study director, Incyte Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04551053
- Sponsor's protocol ID
- INCB 50465-304/LIMBER-304
- Other IDs
- 2020-003415-98
- Status last verified
- Sep 2025
- First submitted
- 11 Sep 2020
- Last updated
- 2 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib
- ClinicalTrials.gov ID
- NCT04551053
- Acronym / sponsor ID
- INCB 50465-304/LIMBER-304
- Conditions
- Myelofibrosis, Primary Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia Vera Myelofibrosis
- Keywords
- INCB050465, ruxolitinib, parsaclisib, LIMBER, LIMBER-304, MF, MPN, Myeloproliferative Neoplasm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to futility.
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Incyte CorporationIndustry (pharma, biotech, devices)
- Study start
- 26 May 2021 (actual)
- Primary completion
- 16 Aug 2023 (actual)
- Study completion
- 21 Aug 2024 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Posted 23 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A : ruxolitinib +parsaclisib | Experimental | Drug: parsaclisib, Drug: ruxolitinibParticipants 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 B : ruxolitinib + placebo | Placebo comparator | Drug: ruxolitinib, Drug: placeboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| parsaclisibAlso: INCB050465parsaclisib will be administered QD orally | Drug | Group A : ruxolitinib +parsaclisib |
| ruxolitinibAlso: Jakafi, Jakaviruxolitinib will be administered BID orally | Drug | Group A : ruxolitinib +parsaclisib, Group B : ruxolitinib + placebo |
| placeboplacebo will be administered QD orally | Drug | Group B : ruxolitinib + placebo |
Primary outcome
Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants)
Time frame: Baseline; Week 24
Participants had an MRI of the upper and lower abdomen and pelvis to determine the spleen volume. A CT scan was substituted for participants who were not candidates for MRI or when MRI was not readily available.
8 secondary outcomes
Percentage of Participants Who Have a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v.4.0 (MFSAF v4.0) Diary
Time frame: Baseline; Week 24
Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary
Time frame: Baseline; Week 24
Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary
Time frame: Baseline; up to Week 24
Overall Survival
Time frame: up to 917 days
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Time frame: up to 917 days
Number of Participants With Any Grade 3 or Higher TEAE
Time frame: up to 917 days
Time to the First ≥25% Reduction in Spleen Volume
Time frame: up to 898 days
Duration of Maintenance of a ≥25% Reduction in Spleen Volume
Time frame: up to 898 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Assad, M.D. study director
Incyte Corporation
177 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing parsaclisib and ruxolitinib in people with Myelofibrosis and Primary Myelofibrosis, run by Incyte Corporation at 177 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in United States, China, Italy, Japan, Spain and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving ≥25% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants) (time frame: Baseline; Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.