A Study of INCB050465 in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a Bruton's Tyrosine Kinase (BTK) Inhibitor ((CITADEL-205))

A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ Inhibitor, in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a BTK Inhibitor (CITADEL-205)

This is a Phase 2, open-label, 2-cohort study designed to evaluate the efficacy and safety of 2 parsaclisib treatment regimens in participants with relapsed or refractory mantle cell lymphoma (MCL) previously treated either with or without a Bruton's tyrosine kinase (BTK) inhibitor.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Institut Jules Bordet
  • La Louviere, Belgium, 07100
    • Hopital de Jolimont
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultní nemocnice Hradec Králové
  • Prague, Czechia, 10034
    • Fakultni Nemocnice Kralovske Vinohadry, Interni Hematologicka Klinika
  • Prague 10, Czechia, 500 05
    • Fakultní nemocnice Královské Vinohrady
  • Prague 2, Czechia, 128 08
    • Charles University General Hospital
• Denmark
  • Aalborg, Denmark, 09000
    • Aalborg University Hospital
  • Aarhus, Denmark, DK-8000
    • Aarhus Universitets Hospital
  • Odense C, Denmark, 05000
    • Odense Universitetshospital (Ouh) (Odense University Hospital)
  • Roskilde, Denmark, 04000
    • Zealand University Hospital
• France
  • Bobigny, France, 93000
    • Avicenne Hospital
  • Clermont-ferrand, France, 63230
    • Chu de Clermont - Ferrand- Hospital Estaing
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Grenoble, France, 38043
    • University Hospital Grenoble
  • La Roche Sur Yon, France, 85925
    • Centre Hospitalier Departemental - La-Roche-Sur-Yon - Les Oudairies
  • La Tronche, France, 38700
    • Centre Hospitalier Universitaire de Grenoble
  • Le Chesnay, France, 78157
    • Centre Hospitalier de Versailles
  • Lyon, France, 69008
    • Hospices Civils de Lyon Centre Hospitalier Lyon Sud
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75010
    • Hopital Saint-Louis
  • Paris, France, 75013
    • H�Pital Universitaire Piti�-Salp�Tri�Re
  • Pierre-Bénite Cedex, France, 69310
    • Centre Hospitalier Lyon-Sud
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Tours, France, 37044
    • Chru Hopitaux de Tours, Hospital Bretonneau
  • Villejuif Cedex, France, 94805
    • Institute Gustave Roussy (Igr)
• Germany
  • Augsburg, Germany, 86150
    • Praxis Brudler, Heinrich, Bangerter
  • Essen, Germany, 45122
    • Universitaetsklinikum Essen
  • Essen, Germany, 45147
    • Universit�Tsklinikum Essen
  • Giessen, Germany, 35392
    • Justus-Liebig University
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • Moenchengladbach, Germany, 41063
    • Kliniken Maria Hilf
  • Munchen, Germany, 80634
    • Rotkreuzklinikum Munich
  • ULM, Germany, 89081
    • Universit�Tsklinikum Ulm
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center Ein Karem Hadassah
  • Jerusalem, Israel, 90000
    • Hadassah Hebrew University Medical Center
  • Petach Tikva, Israel, 4841492
    • Rabin Medical Center - Beilinson Hospital
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • Centro Ricerche Cliniche
  • Catania, Italy, 95123
    • Azienda Policlinico Vittorio Emanuele
  • Milano, Italy, 20162
    • Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 22162
    • Ospedale Niguarda Cà Granda
  • Modena, Italy, 41124
    • A.O.U. di Modena - Policlinico
  • Napoli, Italy, 80131
    • A.O.U. Federico II
  • Novara, Italy, 28100
    • AOU Maggiore della Carità
  • Palermo, Italy, 90146
    • Ospedali Riuniti Villa Sofia Cervello
  • Rome, Italy, 00161
    • Sapienza University
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
  • Torino, Italy, 10126
    • Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
  • MI
    • Milano, MI, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
• Poland
  • Bielsko-biala, Poland, 43-300
    • Beskidzkie Centrum Onkologii Im.Jana Pawla Ii
  • Brzozow, Poland, 36-200
    • Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
  • Gdansk, Poland, 80-952
    • University Clinical Center
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Tomaszow Mazowiecki, Poland, 97-200
    • Nu-Med Centrum Diagnostykii I Terapii Onkologicznej
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall D Hebron
  • Barcelona, Spain, 08221
    • Hospital Universitari Mutua Terrassa
  • Barcelona, Spain, 08916
    • Institut Catala D Oncologia
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 De Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Madrid, Spain, 28033
    • MD Anderson Cancer Centre Madrid
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer
  • Pamplona, Spain, 31008
    • Complejo Hospitalario de Navarra
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Sevilla, Spain, 41005
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Valencia, Spain, 46026
    • Hospital Universitario Y Politecnic La Fe
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals (UCLH)
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • California
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Center-Aurora
  • Florida
    • Brooksville, Florida, United States, 34613
      • ASCLEPES Research Centers
    • Tampa, Florida, United States, 33647
      • Moffitt Cancer Center
    • Winter Haven, Florida, United States, 33880
      • Bond & Steele Clinic, P.A.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Niles, Illinois, United States, 60714
      • Illinois Cancer Specialists
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic Hematology
  • New York
    • New Hyde Park, New York, United States, 11042
      • Clinical Research Alliance, Inc.
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care, Inc.
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente - Northwest
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Washington
    • Yakima, Washington, United States, 98902
      • Yakima Valley Memorial Hospital/North Star

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women, aged 18 years or older.
• Documented failure to achieve at least partial response (PR) with, or documented disease progression after, the most recent treatment regimen.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

Exclusion Criteria:

• History of central nervous system lymphoma (either primary or metastatic).
• Prior treatment with idelalisib, other selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors, or a pan PI3K inhibitor.
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of first dose of study treatment.
• Active graft-versus-host disease.
• Liver disease: Participants positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for hepatitis B virus-deoxyribonucleic acid (HBV-DNA). Participants positive for anti-hepatitis C virus (HCV) antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Treatment A (Exposed to Ibrutinib); Participants received parsaclisib 20 mg tablets, orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.	Drug: Parsaclisib; Parsaclisib tablets administered orally with water and without regard to food.; Other Names: INCB050465
Experimental: Cohort 1: Treatment B (Exposed to Ibrutinib); Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.	Drug: Parsaclisib; Parsaclisib tablets administered orally with water and without regard to food.; Other Names: INCB050465
Experimental: Cohort 2: Treatment A (Bruton's Tyrosine Kinase Inhibitor Naïve); Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks. Participants who had not received a BTK inhibitor previously were included in this group.	Drug: Parsaclisib; Parsaclisib tablets administered orally with water and without regard to food.; Other Names: INCB050465
Experimental: Cohort 2: Treatment B (Bruton's Tyrosine Kinase Inhibitor Naïve); Participants received parsaclisib 20 mg tablets, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks. Participants who had not received a BTK inhibitor previously were included in this group.	Drug: Parsaclisib; Parsaclisib tablets administered orally with water and without regard to food.; Other Names: INCB050465

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign5mm×5mm as default;if no longer visible,0×0mm.Node>5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by>50%in length beyond normal.4.No new lesions.	Up to approximately 165 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR=time from first documented evidence of CR or PR until disease progression or death from any cause among participants who achieve an objective response as determined by IRC. Criteria for CR: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative. The criteria for PR included: 1.Lymph nodes and extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node >5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen must have regressed by >50% in length beyond normal. 4.No new lesions.	Up to approximately 165 weeks
Complete Response Rate (CRR)	CRR is defined as the percentage of participants with a CR as defined by response criteria for lymphomas, as determined by an IRC. The criteria for CR included: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative.	Up to approximately 165 weeks
Progression-Free Survival (PFS)	PFS is defined as the time from the date of the first dose of study treatment until the earliest date of disease progression as determined by radiographic disease assessment provided by an IRC, or death from any cause.	Up to approximately 165 weeks
Overall Survival (OS)	OS is defined as the time from the date of the first dose of study treatment until death from any cause.	Up to approximately 165 weeks
Best Percent Change From Baseline in Target Lesion Size	Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase if no decrease available, from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last nonmissing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement.	Up to approximately 165 weeks
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug regardless of starting new anti-lymphoma therapy. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or may require medical or surgical intervention.	From first dose of study drug up to approximately 165 weeks

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Fred Zheng, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2017
• Primary Completion (Actual): March 3, 2021
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: July 27, 2017
• First Submitted That Met QC Criteria: July 27, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: non-Hodgkin lymphoma; Mantle cell lymphoma; Bruton's tyrosine kinase (BTK); phosphatidylinositol 3-kinase (PI3K)
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell
• Other Study ID Numbers: INCB 50465-205 (CITADEL-205); Parsaclisib (Other Identifier: Incyte Corporation); 2017-003148-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be made available to interested researchers after the end of study, a thorough analysis, and the publication of the data in the clinical study report (CSR). As required, results of the data will be posted to ClinicalTrials.gov. Upon request, individual investigators may obtain IPD from the sponsor. The format for data delivery will be determined between sponsor and investigator.
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No