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

Sponsor
Incyte Corporation (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04551066
Collaborator
(none)
440
Enrollment
165
Locations
2
Arms
59.9
Anticipated Duration (Months)
2.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 × 109/L vs 50 to < 100 × 109/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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
440 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Triple blind
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Combination of PI3Kδ Inhibitor Parsaclisib and Ruxolitinib in Participants With Myelofibrosis
Actual Study Start Date :
May 27, 2021
Anticipated Primary Completion Date :
Nov 22, 2023
Anticipated Study Completion Date :
May 23, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A : parsaclisib + ruxolitinib

Participants will receive parsaclisib and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.

Drug: parsaclisib
parsaclisib will be administered QD orally
Other Names:
  • INCB050465

    • Drug: ruxolitinib
    ruxolitinib will be administered BID orally
    Other Names:
  • Jakafi
  • Jakavi

    		•
    Placebo Comparator: Group B : placebo + ruxolitinib

    Participants will receive placebo and ruxolitinib starting from Day 1 for the duration of study, ruxolitinib dose will be determined by baseline platelet count.

    Drug: ruxolitinib
    ruxolitinib will be administered BID orally
    Other Names:
  • Jakafi
  • Jakavi

    • Drug: placebo
    placebo will be administered QD orally

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of participants achieving targeted reduction in spleen volume [Baseline to Week 24]

      Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

    Secondary Outcome Measures

    1. Proportion of participants who have a targeted reduction in Total Symptom Score (TSS) [Baseline to Week 24]

      Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

    2. Change in TSS [Baseline to Week 24]

      Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

    3. Time to the first ≥ 50% reduction in TSS [Baseline to Week 24]

      Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.

    4. Overall Survival (OS) [Up to approximately 36 months]

      OS is defined as randomization date to death due to any cause.

    5. Number of Treatment Emergent Adverse Events (TEAE) [Up to approximately 36 months]

      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.

    6. Time of onset of targeted reduction in spleen volume [Baseline to Week 144]

      Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

    7. Duration of maintenance of targeted reduction in spleen volume [Baseline to Week 144]

      Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alaska Oncology Anchorage Alaska United States 99508
    2 Mayo Clinic Rochester Phoenix Arizona United States 85054
    3 Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center Berkeley California United States 94704
    4 CCARE Fresno California United States 93720
    5 California Research Institute (Cri) Los Angeles California United States 90027-6005
    6 UCLA School of Medicine Los Angeles California United States 90095-3075
    7 Scripps Clinic San Diego California United States 92103
    8 Coastal Integrated Cancer Care - Cicc San Luis Obispo California United States 93401
    9 Stamford Hospital - Medical Oncology Hematology Stamford Connecticut United States 06904
    10 Georgetown University Washington District of Columbia United States 20057
    11 Emory University Atlanta Georgia United States 30322
    12 University of Kansas Hospital Authority Westwood Kansas United States 66205
    13 University of Kentucky - Markey Cancer Center Lexington Kentucky United States 40536
    14 Tulane University New Orleans Louisiana United States 70112
    15 Johns Hopkins University Baltimore Maryland United States 21287
    16 Midamerica Cancer Care Kansas City Missouri United States 64114
    17 New Jersey Hematology Oncology Associates Llc Brick New Jersey United States 08724
    18 Morristown Medical Center - Atlantic Health System Morristown New Jersey United States 07960
    19 Montefiore Medical Center Bronx New York United States 10467
    20 Roswell Park Cancer Institute Buffalo New York United States 14263
    21 Westchester Medical Center Advanced Oncology and Infusion Center Hawthorne New York United States 10532
    22 Mount Sinai School of Medicine New York New York United States 10029
    23 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    24 Duke Cancer Center Durham North Carolina United States 27710
    25 Wake Forest Baptist Medical Center Winston-Salem North Carolina United States 27157
    26 Oregon Health & Science University Columbus Ohio United States 43210
    27 Kaiser Permanente - Northwest Portland Oregon United States 97227
    28 Avera Cancer Institute Sioux Falls South Dakota United States 57103
    29 Texas Oncology - Baylor Sammons Cancer Center Dallas Texas United States 75246-2092
    30 Renovatio Clinical Houston Texas United States 77005
    31 Kelsey Seybold Clinic Houston Texas United States 77025
    32 Houston Methodist Hospital Houston Texas United States 77030
    33 Providence Regional Medical Center Everett Everett Washington United States 98201
    34 Seattle Cancer Care Alliance Seattle Washington United States 98109
    35 Ordensklinikum Linz Gmbh Elisabethinen Linz Austria 04020
    36 Universitaetsklinikum St. Poelten St. Poelten Austria 03100
    37 Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse Wien Austria 01140
    38 Hanusch-Krankenhaus Wiener Gebietskrankenkasse Wien Austria 01140
    39 A.Z. St.-Jan A.V. Brugge Belgium 08000
    40 Cliniques Universitaires Ucl Saint-Luc Brussels Belgium 01000
    41 Cliniques Universitaires Ucl Saint-Luc Brussels Belgium 1000
    42 Grand Hospital de Charleroi Charleroi Belgium 06000
    43 Jessa Ziekenhuis Hasselt Belgium 03500
    44 AZ DELTA Roeselare Belgium 08800
    45 Peking University People'S Hospital (Pkuph) - Institute of Hematology Beijing China 100044
    46 Peking University Third Hospital Beijing China 100091
    47 The First Hospital of Jilin University Changchun China 130021
    48 Xiangya Hospital Central South University Changsha China 410008
    49 Fujian Medical University Union Hospital Fuzhou China 350001
    50 Guangdong Provincial of People Hospital Guangzhou China 510080
    51 Nanfang Hospital Guangzhou China 510515
    52 The First Affiliated Hospital of Zhejiang University Hangzhou China 310003
    53 Harbin Institute of Hematology and Oncology Harbin China 150010
    54 The Affiliated Hospital of Inner Mongolia Medical University Hohhot China 10050
    55 Jinan Central Hospital Jinan China 250013
    56 The First Hospital of Lanzhou University Lanzhou China 730000
    57 Lanzhou University Second Hospital Lanzhou China 730030
    58 Jiangxi Provincial of People Hospital Nanchang China 330000
    59 The First Affiliated Hospital of Nanchang University Nanchang China 330006
    60 Jiangsu Province Hospital Nanjing China 210029
    61 Shenzhen University Hospital Shenzhen China 518055
    62 Tianjin Medical University General Hospital Tianjin China 300052
    63 Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology Wuhan China 430022
    64 Yantai Yuhuangding Hospital Yantai China 264000
    65 Henan Provincial Peoples Hospital Zhengzhou China 450003
    66 Aalborg University Hospital Aalborg Denmark 9000
    67 Odense University Hospital Odense Denmark 5000
    68 Helsinki University Central Hospital Helsinki Finland FI-00029
    69 Centre Hospitalier Universitaire Grenoble Alpes (Chu Grenoble Alpes) - Hopital Albert Michallon La Tronche France 38700
    70 Centre Hospitalier de Versailles - Hopital Andre Mignot Le Chesnay France 78157
    71 Chu Limoges - Hopital Dupuytren Limoges France 87042
    72 Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu Nantes France 44093
    73 Chu Nimes Nimes France 30900
    74 Ap-Hp Groupe Hospitalier Saint-Louis Lariboisiere Fernand-Widal Site Saint Louis (Paris) Paris France 75010
    75 Hospices Civils de Lyon Centre Hospitalier Lyon Sud Pierre-benite France 69495
    76 Hospital de La Miletrie Poitiers France 86021
    77 Chu de Rennes - Hospital Pontchaillou Rennes France 35033
    78 Universitatsklinikum Halle (Saale) Halle (saale) Germany 06120
    79 Universitaetsmedizin Rostock Rostock Germany 18057
    80 Assaf Harofeh Medical Center Beer Yaaqov Israel 70300
    81 Rambam Health Care Campus Haifa Israel 31999
    82 Hadassah Hebrew University Medical Center Ein Karem Hadassah Jerusalem Israel 91120
    83 Davidoff Cancer Center Rabin Medical Center Petah-tikva Israel 49100
    84 Kaplan Medical Center Rehovot Israel 76100
    85 Tel Aviv Sourasky Medical Center Tel Aviv-yafo Israel 64239
    86 Assuta Ramat Hahayal Tel Aviv Israel 69710
    87 Lstituto Di Ematologia Lorenzo Ea.Seragnoli Universita Degli Studi Di Bologna - Policlinico S. Or Bologna Italy 40138
    88 Azienda Policlinico Vittorio Emanuele Catania Italy 95123
    89 Universita Degli Studi Di Genova - Facolta Di Medicina E Chirurgia Genova Italy 16132
    90 Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Meldola Italy 47014
    91 Fondazione Irccs Ca Granda Ospedale Maggiore Milano Italy 20122
    92 Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele Milan Italy 20132
    93 Universita Di Napoli Federico Ii Napoli Italy 80131
    94 Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello Palermo Italy 90146
    95 Aormn Hospital Hematology and Bmt Center Pesaro Italy 61122
    96 Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli Reggio Calabria Italy 89133
    97 Universita Di Roma Tor Vergata Roma Italy 00133
    98 Universita Di Roma Roma Italy 00161
    99 Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore Roma Italy 00168
    100 Policlinico Universitario Agostino Gemelli Universita Cattolica Del Sacro Cuore Rome Italy 00168
    101 Aou San Giovanni Di Dio E Ruggi D'Aragona Salerno Italy 84131
    102 Azienda Ospedaliera San Giuseppe Moscati Taranto Italy 74123
    103 Azienda Sanitaria Universitaria Friuli Centrale Asu Fc Udine Italy 33100
    104 A.O. Universitaria Ospedale Di Circolo E Fondazione Macchi Varese Italy 21100
    105 Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) Verona Italy 37134
    106 Chiba Cancer Center Chiba Japan 260-8677
    107 University of Yamanashi Hospital Chuo Japan 409-3898
    108 Kyushu University Hospital Fukuoka Japan 812-8582
    109 Japanese Red Cross Society Himeji Hospital Himeji-shi Japan 670-8540
    110 Kansai Medical University Hospital Hirakata Japan 573-1191
    111 Tokai University Hospital Isehara Japan 2591193
    112 Kagoshima University Hospital Kagoshima-shi Japan 890-8520
    113 Hospital of the University of Occupation and Environmental Health Kitakyushu-shi Japan 807-8556
    114 Kobe City Medical Center General Hospital Kobe-shi Japan 650-0047
    115 University of Miyazaki Hospital Miyazaki Japan 889-1692
    116 Japanese Red Cross Nagoya Daini Hospital Nagoya-shi Japan 453-8511
    117 Ogaki Municipal Hospital Ogaki Japan 5038502
    118 Osaka Metropolitan University Hospital Osaka Japan 545-8585
    119 Dokkyo Medical University Saitama Medical Center Saitama Japan 343-8555
    120 Hokuyukai Sapporo Hokuyu Hospital Sapporo Japan 003-0006
    121 Tohoku University Hospital Sendai Japan 980-8574
    122 Juntendo University Hospital Tokyo Japan 113-8431
    123 Mie University Hospital TSU Japan 514-0001
    124 Samsung Medical Center Seoul Korea, Republic of 06351
    125 THE CATHOLIC UNIVERSITY OF KOREA SEOUL ST. MARY�S HOSPITAL Seoul Korea, Republic of 06591
    126 Seoul National University Hospital Seoul Korea, Republic of 3080
    127 Wonju Severance Christian Hospital Wonju Korea, Republic of 26426
    128 Haukeland University Hospital Bergen Norway 05021
    129 Akershus University Hospital Lorenskog Norway 01478
    130 Samodzielny Publiczny Szpital Kliniczny Im. Andrzeja Mielckiego Katowice Poland 40-027
    131 Pratia Hematologia Katowice Katowice Poland 41-519
    132 Sp Zoz Szpital Uniwersytecki Krakow Poland 31-501
    133 Samodzielny Publiczny Szpital Kliniczny Nr 1 Lublin Poland 20-081
    134 Institute of Hematology and Transfusion Medicine Warszawa Poland 02-776
    135 Hospital General Unviersitario de Alicante Alicante Spain 3010
    136 Ico Hospital Germans Trias I Pujol Badalona Spain 8916
    137 Hospital Del Mar Barcelona Spain 08003
    138 Hospital General Universitario Vall D Hebron Barcelona Spain 08035
    139 Ico-Hospital Duran I Reynals Barcelona Spain 08908
    140 Institut Catala Doncologia Ico - Hospital Duran I Reynals Location Barcelona Spain 08908
    141 Ico Hospital Germans Trias I Pujol Barcelona Spain 08916
    142 Hospital Del Mar Barcelona Spain 8003
    143 Hospital de Basurto Bilbao Spain 48013
    144 Hospital Universitario Virgen de La Arrixaca El Palmar Spain 30120
    145 Hospital Universitario Virgen de Las Nieves Granada Spain 18014
    146 Hospital Universitario Insular de Gran Canaria Las Palmas de Gran Canaria Spain 35010
    147 Fundacian Jimnez Diaz Madrid Spain 28040
    148 Hospital Universitario 12 de Octubre Madrid Spain 28041
    149 Hospital General Universitario Morales Meseguer Murcia Spain 30008
    150 Hospital Clinico Universitario de Salamanca Salamanca Spain 37007
    151 Hospital Universitari I Politecnic La Fe Valencia Spain 46000
    152 Hospital Universitario Doctor Peset Valencia Spain 46017
    153 Baskent University Adana Hospital Adana Turkey 01250
    154 Gazi University Hospital Gazi University Faculty of Medicine Ankara Turkey 06500
    155 Istanbul Medipol Universitesi Ibagcilar Medipol Mega Universitesi Hastanesi Istanbul Turkey 34214
    156 Baskent University Istanbul Hospital Istanbul Turkey
    157 Ege University Hospital Izmir Turkey 35040
    158 Dokuz Eylul University Izmir Turkey 35340
    159 Ondokuz Mayis University Medicine Faculty Samsun Turkey 55200
    160 United Lincolnshire Hospitals Boston United Kingdom PE21 9QS
    161 Gloucestershire Royal Hospital Gloucester United Kingdom GL1 3NN
    162 Barts Health NHS Trust - St. Bartholomews Hospital London United Kingdom EC1A 7BE
    163 University College London Hospitals Nhs Foundation Trust London United Kingdom NW1 2BU
    164 Sheffield Teaching Hospitals Nhs Foundation Trust - Weston Park Hospital Sheffield United Kingdom S5 7AT
    165 University Hospital of North Midlands Nhs Trust Stoke-on-trent United Kingdom ST4 6QG

    Sponsors and Collaborators

    • Incyte Corporation

    Investigators

    • Study Director: Albert Assad, M.D, Incyte Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT04551066
    Other Study ID Numbers:
    • INCB 50465-313/LIMBER-313
    • NCT04816578
    First Posted:
    Sep 16, 2020
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Incyte Corporation
    INCB050465
    ruxolitinib
    parsaclisib
    LIMBER
    MF
    Myelofibrosis
    Myeloproliferative Neoplasms
    Myoproliferative Neoplasms
    Additional relevant MeSH terms:
    Polycythemia Vera
    Primary Myelofibrosis
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential

    Study Results

    No Results Posted as of Jul 26, 2022