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

Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04551053
• Other study ID #: INCB 50465-304/LIMBER-304
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 26, 2021
• Est. completion date: July 31, 2024

Study information

• Verified date: May 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Other known NCT identifiers

• NCT04816565

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 177
• Est. completion date: July 31, 2024
• Est. primary completion date: August 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelofibrosis
• Polycythemia
• Polycythemia Vera
• Post Essential Thrombocythemia Myelofibrosis
• Post Polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• parsaclisib
parsaclisib will be administered QD orally
• ruxolitinib
ruxolitinib will be administered BID orally
• placebo
placebo will be administered QD orally

Locations

Country	Name	City	State
Austria	Hanusch-Krankenhaus Wiener Gebietskrankenkasse	Wien
Belgium	A.Z. St.-Jan A.V.	Brugge
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	AZ Delta	Roeselare
Belgium	Chu Ucl Namur University Hospital Mont-Godinne	Yvoir
China	Peking University Third Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing
China	Peking University People'S Hospital (Pkuph) - Institute of Hematology	Beijing SHI
China	The First Hospital of Jilin University	Changchun
China	The First Peoples Hospital of Changzhou	Changzhou
China	Fujian Medical University Union Hospital	Fuzhou
China	Nanfang Hospital	Guangzhou
China	The First Affiliated Hospital of Zhejiang University	Hangzhou
China	Harbin Institute of Hematology and Oncology	Harbin
China	University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)	Hefei
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot
China	Jinan Central Hospital	Jinan
China	The Second Affiliated Hospital of Kunming Medical University	Kunming
China	Lanzhou University Second Hospital	Lanzhou
China	The First Hospital of Lanzhou University	Lanzhou
China	Jiangxi Provincial of People Hospital	Nanchang
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	Jiangsu Province Hospital	Nanjing
China	The Affiliated Hospital of Qingdao University	Qingdao
China	The First Hospital of China Medical University	Shenyang
China	Shenzhen University Hospital	Shenzhen
China	Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Pek	Tianjin
China	Tianjin Medical University General Hospital	Tianjin
China	Tongji Hospital Huazhong University of Science and Technology	Wuhan
China	Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology	Wuhan
China	The Second Affiliated Hospital of Xi an Jiaotong University	Xi'an
China	Yantai Yuhuangding Hospital	Yantai
China	Henan Cancer Hostipal	Zhengzhou
China	Henan Provincial Peoples Hospital	Zhengzhou
Finland	Helsinki University Central Hospital	Helsinki
France	Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon	La Tronche
France	Chu de Limoges	Limoges Cedex
France	CHU Limoges - Hopital Duputren	Limoges Cedex
France	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes
France	Chu Nimes	Nimes
France	Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris)	Paris
France	Hospital Saint Antoine	Paris
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre-Benite
France	Institut Universitaire Du Cancer de Toulouse Oncopole	Toulouse
France	Chu Vandoeuvre-Les-Nancy Hopital Brabois	Vandoeuvre-les-nancy
Germany	Universitatsklinikum Bonn Aoer	Bonn
Germany	Universitaetsmedizin Greifswald	Greifswald
Germany	Universitatsklinikum Halle (Saale)	Halle (saale)
Germany	Universitaetsmedizin Rostock	Rostock
Hungary	Semmelweis Egyetem	Budapest
Hungary	Markhot Ferenc Korhaz	Eger
Hungary	Petz Aladar County Teaching Hospital	Gyor
Israel	Samson Assuta Ashdod University Hospital	Ashdod
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Hebrew University Medical Center Ein Karem Hadassah	Jerusalem
Israel	Kaplan Medical Center	Rehovot
Israel	Assuta Ramat Hahayal	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino
Italy	Aou Policlinico Consorziale Di Bari	Bari
Italy	Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or	Bologna
Italy	Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi	Catania
Italy	University of Florence	Florence
Italy	Irccs Azienda Ospedaliera Universitaria San Martino	Genova
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore	Milano
Italy	Universita Di Napoli Federico Ii	Napoli
Italy	Azienda Ospedaliero Universitaria Maggiore Della Carita Di Novara	Novara
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo
Italy	Ospedale S.Maria Della Misericordia	Perugia
Italy	Ospedale S.Maria Della Misericordia	Perugia
Italy	Presidio Ospedaliero Pescara	Pescara
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli	Reggio Calabria
Italy	Ospedale Sant. Eugenio	Roma
Italy	Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Roma
Italy	Univ. Di Roma Facolta Di Armacia E Medicina	Roma
Italy	Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Rome
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte	Siena
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
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	Juntendo University Hospital	Izunokuni
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-shi
Japan	Kumamoto Shinto General Hospital	Kumamoto-shi
Japan	University of Miyazaki Hospital	Miyazaki
Japan	Japanese Red Cross Nagoya Daini Hospital	Nagoya-shi
Japan	Ogaki Municipal Hospital	Ogaki
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Dokkyo Medical University Saitama Medical Center	Saitama
Japan	Hokuyukai Sapporo Hokuyu Hospital	Sapporo
Japan	Juntendo University Hospital	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	University of Yamanashi Hospital	Yamanashi
Korea, Republic of	Pusan National University Yangsan Hospital	Busan
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary?S Hospital	Seoul
Norway	Haukeland University Hospital	Bergen
Norway	Akershus University Hospital	Lorenskog
Poland	Pratia Hematologia Katowice	Katowice
Poland	Pratia Hematologia Katowice	Katowice
Poland	Samodzielny Publiczny Zoz Szpital Uniwersytecki W Krakowie	Krakow
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1	Lublin
Poland	Institute of Hematology and Transfusion Medicine	Warszawa
Romania	Spitalul Clinic Coltea - Clinica Hematologie	Bucharest,
Romania	Spitalul Clinic Judetean de Urgenta Targu Mures	Targu
Spain	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	Institut Catala Doncologia Ico - Hospital Duran I Reynals Location	Barcelona
Spain	Hospital Universitario Insular de Gran Canaria	Las Palmas de Gran Canaria
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Hospital Universitario Virgen de La Arrixaca	Murcia
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitari I Politecnic La Fe	Valencia
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung City
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University (Ncku) Hospital	Tainan
Turkey	Baskent University Adana Hospital	Adana
Turkey	Gazi University Hospital Gazi University Faculty of Medicine	Ankara
Turkey	Baskent University Istanbul Hospital	Istanbul
Turkey	Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi	Istanbul
Turkey	Ege University Hospital	Izmir
Turkey	Ondokuz Mayis University Medicine Faculty	Samsun
United Kingdom	Grampian Health Board	Aberdeen
United Kingdom	United Lincolnshire Hospitals	Boston
United Kingdom	Gloucestershire Royal Hospital	Gloucester
United Kingdom	University College London Hospitals Nhs Foundation Trust	London
United Kingdom	James Cook University Hospital	Middlesbrough
United States	Emory University	Atlanta	Georgia
United States	Augusta University - Medical College of Georgia	Augusta	Georgia
United States	Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New Jersey Hematology Oncology Associates Llc	Brick	New Jersey
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	Advent Health Hendersonville Park Ridge Hospital Hendersonville	Clyde	North Carolina
United States	Oregon Health & Science University	Columbus	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke Cancer Center	Durham	North Carolina
United States	Providence Regional Medical Center Everett	Everett	Washington
United States	CCARE	Fresno	California
United States	Westchester Medical Center Advanced Oncology	Hawthorne	New York
United States	Kelsey Seybold Clinic	Houston	Texas
United States	Renovatio Clinical	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Midamerica Cancer Care	Kansas City	Missouri
United States	California Research Institute (Cri)	Los Angeles	California
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Morristown Medical Center - Atlantic Health System	Morristown	New Jersey
United States	Tulane University	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Emad Ibrahim Md Inc	Redlands	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	District of Columbia
United States	University of Kansas Hospital Authority	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  China,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Norway,  Poland,  Romania,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 24
Secondary	Proportion of participants who have a targeted reduction in Total Symptom Score (TSS)	Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Change in TSS	Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Time to the first = 50% reduction in TSS	Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Overall Survival (OS)	OS is defined as randomization date to death due to any cause	Up to approximately 36 months
Secondary	Number of Treatment Emergent Adverse Events (TEAE)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 35 days after last dose of study drug.	Up to approximately 36 months
Secondary	Time of onset of targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 108
Secondary	Duration of maintenance of targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 108

External Links

•   Related Info