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

Myelofibrosis Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04551066
• Other study ID #: INCB 50465-313/LIMBER-313
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 27, 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 of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis.

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.

Other known NCT identifiers

• NCT04816578

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 252
• Est. completion date: July 31, 2024
• Est. primary completion date: August 3, 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.

• 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

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	Ordensklinikum Linz Gmbh Elisabethinen	Linz
Austria	Universitaetsklinikum St. Poelten	Saint P�LTEN
Austria	Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse	Wien
Austria	Hanusch-Krankenhaus Wiener Gebietskrankenkasse	Wien
Belgium	A.Z. St.-Jan A.V.	Brugge
Belgium	Cliniques Universitaires Ucl Saint-Luc	Brussels
Belgium	Grand Hospital de Charleroi	Charleroi
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	AZ DELTA	Roeselare
China	Affiliated Hospital of Hebei University	Baoding
China	Peking University Third Hospital	Beijing
China	Peking University People'S Hospital (Pkuph) - Institute of Hematology	Beijing SHI
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	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	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
Denmark	Aalborg University Hospital	Aalborg
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Central Hospital	Helsinki
France	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	Nimes
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-benite
France	Hospital de La Miletrie	Poitiers
France	Chu de Rennes - Hospital Pontchaillou	Rennes
France	Centre Hospitalier de Roubaix	Roubaix
Germany	Universitatsklinikum Halle (Saale)	Halle (saale)
Germany	Klinikum Kassel Gmbh	Kassel
Germany	Universitatsklinikum Magdeburg A.O.R.	Magdeburg
Germany	Universitaetsmedizin Rostock	Rostock
Israel	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	Assuta Ramat Hahayal	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv-yafo
Italy	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	Milano
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	Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore	Roma
Italy	Universita Di Roma	Roma
Italy	Universita Di Roma Tor Vergata	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
Japan	Chiba Cancer Center	Chiba
Japan	University of Yamanashi Hospital	Chuo
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-shi
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	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-shi
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
Korea, Republic of	Wonju Severance Christian Hospital	Wonju
Norway	Haukeland University Hospital	Bergen
Norway	Akershus University Hospital	L�RENSKOG
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Pratia Hematologia Katowice	Katowice
Poland	Samodzielny Publiczny Szpital Kliniczny Im. Andrzeja Mielckiego	Katowice
Poland	Sp Zoz Szpital Uniwersytecki	Krakow
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1	Lublin
Poland	Institute of Hematology and Transfusion Medicine	Warszawa
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	Ico Hospital Germans Trias I Pujol	Barcelona
Spain	Ico-Hospital Duran I Reynals	Barcelona
Spain	Institut Catala Doncologia Ico - Hospital Duran I Reynals Location	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
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	Dokuz Eylul University	Izmir
Turkey	Ege University Hospital	Izmir
Turkey	Ondokuz Mayis University Medicine Faculty	Samsun
United Kingdom	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 States	Alaska Oncology and Hematology	Anchorage	Alaska
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
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	Roswell Park Cancer Institute	Buffalo	New York
United States	Ohio State University	Columbus	Ohio
United States	Texas Oncology-Baylor Sammons Cancer 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 and Infusion Center	Hawthorne	New York
United States	Houston Methodist Hospital	Houston	Texas
United States	Kelsey Seybold Clinic	Houston	Texas
United States	Midamerica Cancer Care	Kansas City	Missouri
United States	University of Kentucky-Markey Cancer Center	Lexington	Kentucky
United States	California Research Institute (Cri)	Los Angeles	California
United States	UCLA School of Medicine	Los Angeles	California
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	Mayo Clinic Rochester	Phoenix	Arizona
United States	Kaiser Permanente-Northwest	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Scripps Clinic	San Diego	California
United States	Coastal Integrated Cancer Care-Cicc	San Luis Obispo	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Renovatio Clinical	Spring	Texas
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
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  China,  Denmark,  Finland,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Norway,  Poland,  Spain,  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 144
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 144

External Links

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