A Study of INCB050465 in Subjects With Relapsed or Refractory Marginal Zone Lymphoma (CITADEL-204)

A Phase 2, Open-Label, 2-Cohort Study of INCB050465, a PI3Kδ Inhibitor, in Subjects With Relapsed or Refractory Marginal Zone Lymphoma With or Without Prior Exposure to a BTK Inhibitor (CITADEL-204)

The purpose of this study is to evaluate the safety and efficacy of two parsaclisib treatment regimens in participants diagnosed with relapsed or refractory marginal zone lymphoma (MZL) who are naive to or were previously treated with a Bruton's tyrosine kinase (BTK) inhibitor.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Rosario, Argentina, S2000KZE
    • Aou Maggiore Della Carita
• Australia
  • Queensland
    • Auchenflower, Queensland, Australia, 04066
      • ICON Cancer Care
  • South Australia
    • Adelaide, South Australia, Australia, 05000
      • Royal Adelaide Hospital
    • North Adelaide, South Australia, Australia, 05006
      • Calvary North Adelaide Hospital
• Belgium
  • Brussels, Belgium, 01200
    • Cliniques Universitaires Ucl Saint-Luc
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• Denmark
  • Aalborg, Denmark, 09000
    • Aalborg University Hospital
  • Roskilde, Denmark, 04000
    • Zealand University Hospital
• France
  • Bobigny, France, 93000
    • Avicenne Hospital
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Limoges Cedex, France, 87042
    • Chu Limoges - Hospital Le Cluzeau
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Paris, France, 75013
    • H�Pital Universitaire Piti�-Salp�Tri�Re
  • Pierre-benite, France, 69495
    • Hospices Civils de Lyon Centre Hospitalier Lyon Sud
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Villejuif, France, 94800
    • Institute Gustave Roussy (Igr)
• Germany
  • Essen, Germany, 45147
    • Universit�Tsklinikum Essen
  • Gottingen, Germany, 37075
    • Universitätsmedizin Göttingen
  • Kiel, Germany, 24105
    • Universit�Tsklinikum Schleswig-Holstein
  • Ludwigshafen, Germany, 67063
    • Klinikum Ludwigshafen
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • ULM, Germany, 89081
    • Universit�Tsklinikum Ulm
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Hebrew University Medical Center Ein Karem Hadassah
  • Petach Tikva, Israel, 4841492
    • Rabin Medical Center - Beilinson Hospital
  • Ramat Gan, Israel, 52621
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • University of Bologna, Institute of Haematology �L. E A. Ser�Gnoli�
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20132
    • Fondazione Centro San Raffaele - Milano
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerardo di Monza
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"
  • Pescara, Italy, 65124
    • Presidio Ospedaliero Pescara
  • Ravenna, Italy, 48121
    • Ospedale Delle Croci - Ematologia Ravenna
  • Rome, Italy, 00161
    • Sapienza University
• Poland
  • Gdansk, Poland, 02-781
    • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
  • Gdansk, Poland, 80-952
    • Szpitale Wojew�Dzkie W Gdyni Sp�?Ka Z Ograniczon? Odpowiedzialno?Ci?
  • Krakow, Poland, 30-510
    • Malopolskie Centrum Medyczne s.c.
  • Warsaw, Poland, 02-776
    • Klinika Transplantacji Komorel Krwiotworczych
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall d Hebron
  • Barcelona, Spain, 08908
    • Ico Institut Catala D Oncologia
  • Madrid, Spain, 28007
    • HGU Gregorio Marañon
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28223
    • Hospital Universitario Quirónsalud Madrid
  • Majadahonda, Spain, 28222
    • Hospital Puerta de Hierro
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Maidstone, United Kingdom, ME16 9QQ
    • Kent Oncology Centre - Maidstone Hospital
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospital
  • Southampton, United Kingdom, SO16 6YD
    • University of Southampton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates
  • California
    • Redondo Beach, California, United States, 90277
      • Torrance Health Association
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Healthcare Hematology-Oncology
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
    • Whittier, California, United States, 90603
      • Loyola University Medical Center
  • Colorado
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital
    • Grand Junction, Colorado, United States, 81501
      • St. Mary'S Hospital Regional Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Miami, Florida, United States, 33147
      • Advanced Pharma CR
    • Plantation, Florida, United States, 33322
      • Boca Raton Clinical Research Medical Inc.
    • Weeki Wachee, Florida, United States, 34607
      • Asclepes Research Centers
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center - Consultants in Hematology
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Clinical Trials of Swla Llc
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Cancer Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Twain
  • New York
    • New Hyde Park, New York, United States, 11042
      • Clinical Research Alliance
    • New York, New York, United States, 10016
      • NYU Cancer Institute
    • Nyack, New York, United States, 10960
      • Hematology Oncology Associates of Rockland
    • White Plains, New York, United States, 10601
      • White Plains Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates Pa
  • Texas
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington - Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women, aged 18 or older (except in South Korea, aged 19 or older).
• Histologically confirmed marginal zone lymphoma, including extranodal, nodal, and splenic subtypes.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the longest transverse diameter and ≥ 1.0 cm in the longest perpendicular diameter.
• Participants with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed.
• Participants must be willing to undergo an incisional or excisional lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue.
• Eastern Cooperative Oncology Group performance status 0 to 2.

Exclusion Criteria:

• Evidence of diffuse large B-cell transformation.
• History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
• Prior treatment with idelalisib, other selective 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 the first dose of study treatment.
• Active graft versus host disease.
• Subjects positive for hepatitis B surface antigen or hepatitis B core antibody will be eligible if they are negative for HBV-DNA. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1- Closed to Further enrollment; Participants who have received prior ibrutinib.	Drug: Parsaclisib; Parsaclisib at the protocol-defined dose.; Other Names: INCB050465
Experimental: Cohort 2; Participants who have not received a prior BTK inhibitor.	Drug: Parsaclisib; Parsaclisib at the protocol-defined dose.; Other Names: INCB050465

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Based on Lugano Classification Criteria	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),assign 5mm×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 161 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 1305 days
Complete Response Rate (CRR) Based on Lugano Classification Criteria	CRR is defined as the percentage of participants with a CR 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 1305 days
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 1305 days
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 2354 days
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 1305 days
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 1980 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2017
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): May 29, 2024

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Marginal zone lymphoma; phosphatidylinositol 3-kinase (PI3K)δ inhibitor; indolent (slow-growing) non-Hodgkin lymphoma B-cell lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: INCB 50465-204 (CITADEL-204); Parsaclisib (Other Identifier: Incyte Corporation); 2017-000970-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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