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

A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib

Sponsors

Lead Sponsor: Incyte Corporation

Source Incyte Corporation
Brief 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.

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.

Overall Status Recruiting
Start Date 2021-05-26
Completion Date 2024-09-29
Primary Completion Date 2023-11-28
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of participants achieving targeted reduction in spleen volume Baseline to Week 24
Secondary Outcome
Measure Time Frame
Proportion of participants who have a targeted reduction in Total Symptom Score (TSS) Baseline to Week 24
Change in TSS Baseline to Week 24
Time to the first ≥ 50% reduction in TSS Baseline to Week 24
Overall Survival (OS) Up to approximately 36 months
Number of Treatment Emergent Adverse Events (TEAE) Up to approximately 36 months
Time of onset of targeted reduction in spleen volume Baseline to Week 108
Duration of maintenance of targeted reduction in spleen volume Baseline to Week 108
Enrollment 212
Condition
Intervention

Intervention Type: Drug

Intervention Name: parsaclisib

Description: parsaclisib will be administered QD orally

Arm Group Label: Group A : ruxolitinib +parsaclisib

Other Name: INCB050465

Intervention Type: Drug

Intervention Name: ruxolitinib

Description: ruxolitinib will be administered BID orally

Intervention Type: Drug

Intervention Name: placebo

Description: placebo will be administered QD orally

Arm Group Label: Group B : ruxolitinib + placebo

Eligibility

Criteria:

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 (eg, danazol, hydroxyurea) 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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Albert Assad, M.D. Study Director Incyte Corporation
Overall Contact

Last Name: Incyte Corporation Call Center (US)

Phone: 1.855.463.3463

Email: [email protected]

Location
Facility: Status:
Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center | Berkeley, California, 94704, United States Recruiting
CCARE | Fresno, California, 93720, United States Recruiting
Emad Ibrahim Md Inc | Redlands, California, 92373, United States Not yet recruiting
Scripps Clinic | San Diego, California, 92103, United States Not yet recruiting
Coastal Integrated Cancer Care - Cicc | San Luis Obispo, California, 93401, United States Recruiting
Stamford Hospital - Medical Oncology Hematology | Stamford, Connecticut, 06904, United States Recruiting
Georgetown University | Washington, District of Columbia, 20057, United States Not yet recruiting
Emory University | Atlanta, Georgia, 30322, United States Not yet recruiting
Augusta University Medical College | Augusta, Georgia, 30912, United States Not yet recruiting
University of Indiana | Indianapolis, Indiana, 46202, United States Not yet recruiting
University of Kansas Hospital Authority | Westwood, Kansas, 66205, United States Recruiting
Tulane University | New Orleans, Louisiana, 70112, United States Recruiting
Massachusetts General Hospital | Boston, Massachusetts, 02114, United States Recruiting
Beth Israel Deaconess | Boston, Massachusetts, 02215, United States Recruiting
Midamerica Cancer Care | Kansas City, Missouri, 64114, United States Recruiting
New Jersey Hematology Oncology Associates Llc | Brick, New Jersey, 08724, United States Recruiting
Morristown Medical Center | Morristown, New Jersey, 07960, United States Not yet recruiting
Montefiore Medical Center | Bronx, New York, 10467, United States Recruiting
Westchester Medical Center Advanced Oncology | Hawthorne, New York, 10532, United States Not yet recruiting
Mount Sinai School of Medicine | New York, New York, 10029, United States Recruiting
Weill Cornell Medical Centers | New York, New York, 10065, United States Not yet recruiting
Duke Cancer Ctr | Durham, North Carolina, 27710, United States Recruiting
Advent Health Hendersonville | Hendersonville, North Carolina, 28792, United States Not yet recruiting
Cleveland Clinic | Cleveland, Ohio, 44195, United States Not yet recruiting
Oregon Health | Portland, Oregon, 97239, United States Not yet recruiting
Hillman Cancer Center | Pittsburgh, Pennsylvania, 15232, United States Not yet recruiting
Texas Oncology - Medical City Dallas | Dallas, Texas, 75230, United States Recruiting
Texas Oncology - Baylor Sammons Cancer Center | Dallas, Texas, 75246-2092, United States Recruiting
UT Southwestern Medical Center | Dallas, Texas, 75390-8565, United States Not yet recruiting
Renovatio Clinical | Houston, Texas, 77005, United States Recruiting
Kelsey Seybold Clinic | Houston, Texas, 77025, United States Recruiting
Providence Regional Medical Center | Everett, Washington, 98201, United States Recruiting
Hanusch-Krankenhaus Wiener Gebietskrankenkasse | Wien, 01140, Austria Recruiting
A.Z. St.-Jan A.V. | Brugge, 08000, Belgium Recruiting
Chu Mont Godinne | Yvoir, 05530, Belgium Recruiting
Beijing Friendship Hospital | Beijing, 100050, China Not yet recruiting
Xuanwu Hospital Capital Medical University | Beijing, 100053, China Not yet recruiting
Peking University Third Hospital | Beijing, 100191, China Not yet recruiting
Peking University of People Hospital | Beijing, 100871, China Not yet recruiting
The First Hospital of Jilin University | Changchun, 130021, China Not yet recruiting
The First Peoples Hospital of Changzhou | Changzhou, 213003, China Not yet recruiting
The Second Affiliated Hospital of Dalian Medical University | Dalian, 116044, China Not yet recruiting
Fujian Medical University Union Hospital | Fuzhou, 350001, China Not yet recruiting
Nanfang Hospital | Guangzhou, 510515, China Not yet recruiting
The First Affiliated Hospital of Zhejiang University | Hangzhou, 310003, China Not yet recruiting
Harbin Institute of Hematology and Oncology | Harbin, 150010, China Not yet recruiting
The First Affiliated Hospital of Anhui Medical University | Hefei, 230022, China Not yet recruiting
University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital) | Hefei, 230022, China Not yet recruiting
The Affiliated Hospital of Inner Mongolia Medical University | Hohhot, 10050, China Not yet recruiting
Jinan Central Hospital | Jinan, 250013, China Not yet recruiting
Shandong Provincial Hospital | Jinan, 250021, China Not yet recruiting
The Second Affiliated Hospital of Kunming Medical University | Kunming, 650101, China Not yet recruiting
The First Hospital of Lanzhou University | Lanzhou, 730000, China Not yet recruiting
Lanzhou University Second Hospital | Lanzhou, 730030, China Not yet recruiting
Jiangxi Provincial of People Hospital | Nanchang, 330000, China Not yet recruiting
The First Affiliated Hospital of Nanchang University | Nanchang, 330006, China Not yet recruiting
Jiangsu Province Hospital | Nanjing, 210029, China Not yet recruiting
The Affiliated Hospital of Qingdao University | Shandong, 266071, China Not yet recruiting
Shanghai Jiao Tong University Ruijin Hospital | Shanghai, 200025, China Not yet recruiting
The First Hospital of China Medical University | Shenyang, 110001, China Not yet recruiting
Shenzhen University Hospital | Shenzhen, China Not yet recruiting
Tianjin Medical University General Hospital | Tianjin, 300052, China Not yet recruiting
Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Pek | Tianjin, 510080, China Not yet recruiting
Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology | Wuhan, 430022, China Not yet recruiting
Tongji Hospital Huazhong University of Science and Technology | Wuhan, 430030, China Not yet recruiting
The Second Affiliated Hospital of Xi an Jiaotong University | Xi'an, 710004, China Not yet recruiting
Yantai Yuhuangding Hospital | Yantai, 264000, China Not yet recruiting
Henan Provincial Peoples Hospital | Zhengzhou, 450003, China Not yet recruiting
Henan Cancer Hostipal | Zhengzhou, 450008, China Not yet recruiting
Helsinki University Central Hospital | Helsinki, FI-00029, Finland Recruiting
Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon | La Tronche, 38700, France Recruiting
CHU Limoges - Hopital Duputren | Limoges Cedex, 87042, France Not yet recruiting
Chu Limoges - Hopital Dupuytren | Limoges, 87042, France Not yet recruiting
Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu | Nantes, 44093, France Recruiting
Chu Nimes | Nimes, 30900, France Recruiting
Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris) | Paris, 75010, France Recruiting
Hospital Saint Antoine | Paris, 75012, France Recruiting
Hospices Civils de Lyon Centre Hospitalier Lyon Sud | Pierre-Benite, 69495, France Not yet recruiting
Institut Universitaire Du Cancer de Toulouse Oncopole | Toulouse, 31059, France Recruiting
Chu Vandoeuvre-Les-Nancy Hopital Brabois | Vandoeuvre-les-nancy, 54500, France Recruiting
Universitatsklinikum Bonn Aoer | Bonn, 53127, Germany Not yet recruiting
Universitaetsmedizin Greifswald | Greifswald, 17475, Germany Recruiting
Universitatsklinikum Halle (Saale) | Halle (saale), 06120, Germany Recruiting
Universitaetsmedizin Rostock | Rostock, 18057, Germany Recruiting
Semmelweis Egyetem | Budapest, 01083, Hungary Recruiting
Markhot Ferenc Korhaz | Eger, 3300, Hungary Recruiting
Petz Aladar Megyei Oktato Korhaz | Gyor, 9024, Hungary Not yet recruiting
Samson Assuta Ashdod University Hospital | Ashdod, 7747629, Israel Not yet recruiting
Rambam Health Care Campus | Haifa, 31999, Israel Not yet recruiting
Hadassah Hebrew University Medical Center Ein Karem | Jerusalem, 910020, Israel Not yet recruiting
Kaplan Medical Center | Rehovot, 76100, Israel Not yet recruiting
Tel Aviv Sourasky Medical Center | Tel Aviv, 64239, Israel Not yet recruiting
Assuta Ramat Hahayal | Tel Aviv, 69710, Israel Not yet recruiting
Azienda Ospedaliera San Giuseppe Moscati | Avellino, 83100, Italy Not yet recruiting
Piazza Giulo Cesare 11 | Bari, 70124, Italy Not yet recruiting
Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or | Bologna, 40138, Italy Recruiting
Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi | Catania, 11111, Italy Not yet recruiting
University of Florence | Florence, 50134, Italy Recruiting
Irccs A.O.U. San Martino - Ist | Genova, 16132, Italy Not yet recruiting
Fondazione Irccs Ca Granda Ospedale Maggiore | Milano, 20122, Italy Recruiting
Universita Di Napoli Federico Ii | Napoli, 80131, Italy Recruiting
Azienda Ospedaliero Universitaria Maggiore Della Carita Di Novara | Novara, 28100, Italy Recruiting
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello | Palermo, 90146, Italy Recruiting
Ospedale S.Maria Della Misericordia | Perugia, 06156, Italy Recruiting
Ospedale S.Maria Della Misericordia | Perugia, 6156, Italy Recruiting
Presidio Ospedaliero Pescara | Pescara, 6156, Italy Not yet recruiting
Azienda Ospedaliero Universitaria Pisana | Pisa, 56126, Italy Not yet recruiting
Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli | Reggio Calabria, 89133, Italy Not yet recruiting
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore | Roma, 00168, Italy Recruiting
Ospedale Sant. Eugenio | Roma, 144, Italy Not yet recruiting
Univ. Di Roma Facolta Di Armacia E Medicina | Roma, 161, Italy Not yet recruiting
Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore | Roma, 168, Italy Recruiting
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte | Siena, 53100, Italy Recruiting
Azienda Ospedaliera San Giuseppe Moscati | Taranto, 74123, Italy Not yet recruiting
Azienda Sanitaria Universitaria Friuli Centrale Asu Fc | Udine, 33100, Italy Recruiting
A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi | Varese, 21100, Italy Not yet recruiting
Kyushu University Hospital | Fukuoka, 812-8582, Japan Recruiting
Japanese Red Cross Society Himeji Hospital | Himeji-shi, 670-8540, Japan Recruiting
Kansai Medical University Hospital | Hirakata, 573-1191, Japan Recruiting
Tokai University Hospital | Isehara, 259-1193, Japan Recruiting
Kagoshima University Hospital | Kagoshima, 890-8520, Japan Recruiting
Kobe City Medical Center General Hospital | Kobe-shi, 650-0047, Japan Recruiting
University of Miyazaki Hospital | Miyazaki, 889-1692, Japan Recruiting
Japanese Red Cross Nagoya Daini Hospital | Nagoya-shi, 453-8511, Japan Recruiting
Ogaki Municipal Hospital | Ogaki, 503-8502, Japan Recruiting
Osaka City University Hospital | Osaka, 545-8585, Japan Recruiting
Dokkyo Medical University Saitama Medical Center | Saitama, 343-8555, Japan Recruiting
Hokuyukai Sapporo Hokuyu Hospital | Sapporo, 003-0006, Japan Recruiting
Juntendo University Hospital | Tokyo, 113-8431, Japan Recruiting
Juntendo University Shizouka | Tokyo, 113-8431, Japan Not yet recruiting
Nippon Medical School Hospital | Tokyo, 113-8603, Japan Recruiting
University of Yamanashi Hospital | Yamanashi, 409-3898, Japan Recruiting
Pusan National University Hospital | Busan-Si, 602-739, Korea, Republic of Not yet recruiting
Seoul National University Hospital | Seoul, 03080, Korea, Republic of Not yet recruiting
Samsung Medical Center | Seoul, 06351, Korea, Republic of Not yet recruiting
The Catholic University of Korea Seoul St. Mary'S Hospital | Seoul, 137-701, Korea, Republic of Not yet recruiting
Haukeland University Hospital | Bergen, 05021, Norway Recruiting
Akershus University Hospital | Lorenskog, 1478, Norway Recruiting
Akershus University Hospital | Lørenskog, 01478, Norway Recruiting
Samodzielny Puliczny Szpital Kliniczny im. Andrzeja Mielckiego | Katowice, 40-027, Poland Not yet recruiting
Pratia Hematologia Katowice | Katowice, 41-081, Poland Not yet recruiting
Pratia Hematologia Katowice | Katowice, 41-519, Poland Recruiting
Sp Zoz Szpital Uniwersytecki | Krakow, 31-501, Poland Recruiting
Institute of Hematology and Transfusion Medicine | Warszawa, 02-776, Poland Not yet recruiting
Spitalul Clinic Coltea - Clinica Hematologie | Bucharest, 30171, Romania Not yet recruiting
Onco Clinic Consult | Craiova, 200094, Romania Not yet recruiting
Spitalul Clinic Judetean de Urgenta Targu Mures | Targu Mures, 54039, Romania Not yet recruiting
Hospital General Unviersitario de Alicante | Alicante, 03010, Spain Recruiting
Ico Hospital Germans Trias I Pujol | Badalona, 08916, Spain Recruiting
Hospital Del Mar | Barcelona, 08003, Spain Recruiting
Hospital General Universitario Vall D Hebron | Barcelona, 08035, Spain Recruiting
Ico-Hospital Duran I Reynals | Barcelona, 08908, Spain Recruiting
Hospital Universitario Insular de Gran Canaria | Las Palmas de Gran Canaria, 35010, Spain Recruiting
Hospital Universitario 12 de Octubre | Madrid, 24041, Spain Recruiting
Fundacion Jimenez Diaz University Hospital | Madrid, 28040, Spain Recruiting
Hospital General Universitario Morales Meseguer | Murcia, 30008, Spain Recruiting
Hospital Universitario Virgen de La Arrixaca | Murcia, 30120, Spain Not yet recruiting
Hospital Clinico Universitario de Salamanca | Salamanca, 37007, Spain Recruiting
Hospital Universitario Virgen Del Rocio | Sevilla, 41013, Spain Active, not recruiting
Hospital Universitari I Politecnic La Fe | Valencia, 46000, Spain Recruiting
Hospital Universitario Doctor Peset | Valencia, 46017, Spain Recruiting
Hospital Universitario Miguel Servet | Zaragoza, 50009, Spain Recruiting
Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City, 83301, Taiwan Not yet recruiting
China Medical University Hospital | Taichung City, 40447, Taiwan Not yet recruiting
National Cheng Kung University (Ncku) Hospital | Tainan City, 70428, Taiwan Not yet recruiting
Baskent University Adana Hospital | Adana, 01250, Turkey Not yet recruiting
Gazi University Hospital | Ankara, 6500, Turkey Not yet recruiting
Bagcilar Medipol Mega University Hospital | Istanbul, 34214, Turkey Not yet recruiting
Istanbul Medipol Universitesi - Bagcilar Medipol Mega Universitesi Hastanesi | Istanbul, 34214, Turkey Not yet recruiting
Baskent University Istanbul Hospital | Istanbul, 34662, Turkey Not yet recruiting
Dokuz Eylul University | Izmir, 35040, Turkey Not yet recruiting
Ege Univ. Hospital | Izmir, 35040, Turkey Not yet recruiting
Ondokuz Mays University Medicine Faculty | Samsun, 55200, Turkey Not yet recruiting
Grampian Health Board | Aberdeen, AB15 6RE, United Kingdom Recruiting
United Lincolnshire Hospitals | Boston, PE21 9QS, United Kingdom Not yet recruiting
Gloucestershire Royal Hospital | Gloucester, GL1 3NN, United Kingdom Recruiting
University College London Hospitals Nhs Foundation Trust | London, NW1 2BU, United Kingdom Not yet recruiting
James Cook University Hospital | Middlesborough, TS4 3BW, United Kingdom Not yet recruiting
Location Countries

Austria

Belgium

China

Finland

France

Germany

Hungary

Israel

Italy

Japan

Korea, Republic of

Norway

Poland

Romania

Spain

Taiwan

Turkey

United Kingdom

United States

Verification Date

2021-10-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Group A : ruxolitinib +parsaclisib

Type: Experimental

Description: 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.

Label: Group B : ruxolitinib + placebo

Type: Placebo Comparator

Description: 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.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Masking Description: Triple blind

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