Clinical trial NCT04551066: To Evaluate the Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis (LIMBER-313)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelofibrosis
Primary Myelofibrosis
Post Essential Thrombocythemia Myelofibrosis
Post Polycythemia Vera Myelofibrosis
Keywords: INCB050465
ruxolitinib
parsaclisib
LIMBER
MF
Myelofibrosis
Myeloproliferative Neoplasms
Myoproliferative Neoplasms
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 252
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: This is a Phase 3, randomized, double-blind study of the combination of the PI3Kδ inhibitor parsaclisib or matching placebo and the JAK1/2 inhibitor ruxolitinib in participants with PMF or secondary MF (PPV-MF or PET-MF) with DIPSS risk category of intermediate or high. Prospective participants must have not received prior MF therapy with a JAK inhibitor or a PI3K inhibitor. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10\^9/L vs 50 to \< 100 × 10\^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs intermediate-1).

Once all enrolled participants completed the week 24 assessments the study will be unblinded and and participants randomized to placebo will have the opportunity to cross over to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of PMF, PPV-MF, or PET-MF.
* DIPSS risk category of intermediate-1, intermediate-2, or high.
* Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit.
* Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form.
* Participants with an ECOG performance status score of 0, 1, or 2.
* Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after. Screening/baseline biopsy specimen must show diagnosis of MF.
* Life expectancy of at least 24 weeks.
* Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

* Prior use of any JAK inhibitor.
* Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).
* Use of experimental drug therapy for MF or any other standard drug (eg, danazol, hydroxyurea) used for MF within 3 months of starting study drug and/or lack of recovery from all toxicities from previous therapy to ≤ Grade 1.
* Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
* Recent history of inadequate bone marrow reserve.
* Inadequate liver and renal function at screening.
* Active bacterial, fungal, parasitic, or viral infection that requires therapy.
* Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.
* Known HIV infection.
* Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.
* Active invasive malignancy over the previous 2 years.
* Splenic irradiation within 6 months before receiving the first dose of study drug.
* Concurrent use of any prohibited medications.
* Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.
* Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.
* Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
* Currently breastfeeding or pregnant.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* History of Grade 3 or 4 irAEs from prior immunotherapy.
* Receipt of any live vaccine within 30 days of the first dose of study drug

Primary outcomes:
measure: Percentage of Participants Achieving ≥35% Reduction in Spleen Volume From Baseline to Week 24 as Measured by Magnetic Resonance Imaging [MRI] (or Computed Tomography [CT] Scan in Applicable Participants)
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: Percentage of Participants Who Had a ≥50% Reduction in Total Symptom Score (TSS) From Baseline to Week 24 as Measured by the Myelofibrosis Symptom Assessment Form v4.0 (MFSAF v4.0) Diary
timeFrame: Baseline; Week 24
measure: Change in TSS From Baseline to Week 24 as Measured by the MFSAF v4.0 Diary
timeFrame: Baseline; Week 24
measure: Time to the First ≥50% Reduction in TSS as Measured by the MFSAF v4.0 Diary
timeFrame: Baseline; up to Week 24
measure: Overall Survival
timeFrame: up to 749 days
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 749 days
measure: Number of Participants With Any Grade 3 or Higher TEAE
timeFrame: up to 749 days
measure: Time of Onset of a ≥35% Reduction in Spleen Volume
timeFrame: up to 749 days
measure: Duration of Maintenance of a ≥35% Reduction in Spleen Volume
timeFrame: up to 749 days
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology
state: Alaska
city: Phoenix
country: United States
facility: Mayo Clinic Rochester
state: Arizona
city: Berkeley
country: United States
facility: Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center
state: California
city: Fresno
country: United States
facility: CCARE
state: California
city: Los Angeles
country: United States
facility: California Research Institute (Cri)
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: San Diego
country: United States
facility: Scripps Clinic
state: California
city: San Luis Obispo
country: United States
facility: Coastal Integrated Cancer Care-Cicc
state: California
city: Stamford
country: United States
facility: Stamford Hospital-Medical Oncology Hematology
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Westwood
country: United States
facility: University of Kansas Hospital Authority
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky-Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Midamerica Cancer Care
state: Missouri
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates Llc
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center-Atlantic Health System
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Hawthorne
country: United States
facility: Westchester Medical Center Advanced Oncology and Infusion Center
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente-Northwest
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Dallas
country: United States
facility: Texas Oncology-Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Kelsey Seybold Clinic
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Spring
country: United States
facility: Renovatio Clinical
state: Texas
city: Everett
country: United States
facility: Providence Regional Medical Center Everett
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Linz
country: Austria
facility: Ordensklinikum Linz Gmbh Elisabethinen
city: Saint Pï¿½LTEN
country: Austria
facility: Universitaetsklinikum St. Poelten
city: Wien
country: Austria
facility: Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse
city: Wien
country: Austria
facility: Hanusch-Krankenhaus Wiener Gebietskrankenkasse
city: Brugge
country: Belgium
facility: A.Z. St.-Jan A.V.
city: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Charleroi
country: Belgium
facility: Grand Hospital de Charleroi
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Roeselare
country: Belgium
facility: AZ DELTA
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing SHI
country: China
facility: Peking University People'S Hospital (Pkuph) - Institute of Hematology
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial of People Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
city: Harbin
country: China
facility: Harbin Institute of Hematology and Oncology
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
city: Jinan
country: China
facility: Jinan Central Hospital
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
city: Nanchang
country: China
facility: Jiangxi Provincial of People Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenzhen
country: China
facility: Shenzhen University Hospital
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Zhengzhou
country: China
facility: Henan Provincial Peoples Hospital
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon
city: LE Chesnay-rocquencourt
country: France
facility: Centre Hospitalier de Versailles - Hopital Andre Mignot
city: Limoges
country: France
facility: Chu Limoges - Hopital Dupuytren
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
city: Nimes
country: France
facility: Chu Nimes
city: Paris
country: France
facility: Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris)
city: Pierre-benite
country: France
facility: Hospices Civils de Lyon Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Hospital de La Miletrie
city: Rennes
country: France
facility: Chu de Rennes - Hospital Pontchaillou
city: Roubaix
country: France
facility: Centre Hospitalier de Roubaix
city: Halle (saale)
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Kassel
country: Germany
facility: Klinikum Kassel Gmbh
city: Magdeburg
country: Germany
facility: Universitatsklinikum Magdeburg A.O.R.
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock
city: Beer Yaaqov
country: Israel
facility: Shamir Medical Center Formerly Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center Ein Karem Hadassah
city: Petah-tikva
country: Israel
facility: Davidoff Cancer Center Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv-yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Ramat Hahayal
city: Bologna
country: Italy
facility: Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or
city: Catania
country: Italy
facility: Azienda Policlinico Vittorio Emanuele
city: Genova
country: Italy
facility: Universita Degli Studi Di Genova - Facolta Di Medicina E Chirurgia
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
city: Milano
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Milan
country: Italy
facility: Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
city: Napoli
country: Italy
facility: Universita Di Napoli Federico Ii
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
city: Pesaro
country: Italy
facility: Aormn Hospital Hematology and Bmt Center
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
city: Roma
country: Italy
facility: Universita Di Roma Tor Vergata
city: Roma
country: Italy
facility: Universita Di Roma
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore
city: Salerno
country: Italy
facility: Aou San Giovanni Di Dio E Ruggi D'Aragona
city: Taranto
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale Asu Fc
city: Varese
country: Italy
facility: A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Himeji-shi
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
city: Isehara
country: Japan
facility: Tokai University Hospital
city: Kagoshima-shi
country: Japan
facility: Kagoshima University Hospital
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupation and Environmental Health
city: Kobe-shi
country: Japan
facility: Kobe City Medical Center General Hospital
city: Kumamoto-shi
country: Japan
facility: Kumamoto Shinto General Hospital
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital
city: Nagoya-shi
country: Japan
facility: Japanese Red Cross Nagoya Daini Hospital
city: Ogaki
country: Japan
facility: Ogaki Municipal Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Saitama
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
city: Sapporo
country: Japan
facility: Hokuyukai Sapporo Hokuyu Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: TSU
country: Japan
facility: Mie University Hospital
city: Yokohama-shi
country: Japan
facility: Yokohama Municipal Citizens Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: THE CATHOLIC UNIVERSITY OF KOREA SEOUL ST. MARYï¿½S HOSPITAL
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Lï¿½RENSKOG
country: Norway
facility: Akershus University Hospital
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Katowice
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Im. Andrzeja Mielckiego
city: Katowice
country: Poland
facility: Pratia Hematologia Katowice
city: Krakow
country: Poland
facility: Sp Zoz Szpital Uniwersytecki
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1
city: Warszawa
country: Poland
facility: Institute of Hematology and Transfusion Medicine
city: Alicante
country: Spain
facility: Hospital General Unviersitario de Alicante
city: Badalona
country: Spain
facility: Ico Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Ico-Hospital Duran I Reynals
city: Barcelona
country: Spain
facility: Institut Catala Doncologia Ico - Hospital Duran I Reynals Location
city: Barcelona
country: Spain
facility: Ico Hospital Germans Trias I Pujol
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
city: Madrid
country: Spain
facility: Fundacian Jimnez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Adana
country: Turkey
facility: Baskent University Adana Hospital
city: Ankara
country: Turkey
facility: Gazi University Hospital Gazi University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi
city: Istanbul
country: Turkey
facility: Baskent University Istanbul Hospital
city: Izmir
country: Turkey
facility: Ege University Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medicine Faculty
city: Boston
country: United Kingdom
facility: United Lincolnshire Hospitals
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
city: London
country: United Kingdom
facility: Barts Health Nhs Trust - St Bartholomews Hospital
city: London
country: United Kingdom
facility: University College London Hospitals Nhs Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital
city: Stoke-on-trent
country: United Kingdom
facility: University Hospital of North Midlands Nhs Trust
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, M.D
role: STUDY_DIRECTOR
References: