A Study of INCB050465 in Relapsed or Refractory Follicular Lymphoma (CITADEL-203)

A Phase 2, Multicenter, Open-Label Study of INCB050465, a PI3Kδ Inhibitor in Relapsed or Refractory Follicular Lymphoma (CITADEL-203)

The purpose of this study is to assess the objective response rate of parsaclisib treatment in participants with relapsed or refractory follicular lymphoma.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst, Australia, 02010
    • St Vincent's Hospital Sydney
  • Victoria
    • St Albans, Victoria, Australia, 03021
      • Western Health
    • Wodonga, Victoria, Australia, 03690
      • Border Medical Oncology
• Canada
  • New Brunswick
    • St. John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Science Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 1P7
      • Santa Cabrini Hospital
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • University Hospital Hradec Kralove
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Prague, Czechia, 10034
    • University Hospital Kralovkse Vinohrady
  • Praha, Czechia, 120 0
    • Univerzita Karlova V Praze 1. Lekarska Fakulta
  • Praha 5, Czechia, 15000
    • Fakultni nemocnice v Motole
• Denmark
  • Aalborg, Denmark, 09000
    • Aalborg University Hospital
  • Odense C, Denmark, 05000
    • Odense Universitetshospital (Ouh) (Odense University Hospital)
• Germany
  • Dresden, Germany, 01307
    • Bag Arnoldstr. Dresden
  • Freiburg, Germany, 79106
    • University Medical Center Freiburg
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • Mannheim, Germany, 68167
    • University Hospital Mannheim
• Hungary
  • Budapest, Hungary, 01085
    • Semmelweis Egyetem
  • Budapest, Hungary, 01122
    • National Institute of Oncology
  • Debrecen, Hungary, 04032
    • University of Debrecen
  • Kaposvar, Hungary, 07400
    • Somogy Medyei Kaposi Mor Oktato Korhaz
• Israel
  • Hadera, Israel, 38100
    • Hillel Yafe Medical Center (Hymc)
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Netanya, Israel, 42150
    • Laniado Hospital Hematology
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Tel Aviv-yafo, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Aviano, Italy, 33081
    • IRCCS Centro di Riferimento Oncologico
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Bologna, Italy, 40126
    • University of Bologna
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • 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
  • San Giovanni Rotondo, Italy, 71013
    • I.R.C.C.S. Casa Sollievo Della Sofferenza
  • Torino, Italy, 10126
    • AOU Citta della Salute e della Scienza di Torino
  • Vicenza, Italy, 36100
    • San Bartolo Hospital
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Opole, Poland, 45-372
    • State Hospital Opole
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
  • Warszawa, Poland, 02-776
    • Institute of Hematology and Transfusion Medicine
• Spain
  • Barcelona, Spain, 08035
    • Hospital General Universitari Vall D Hebron
  • Barcelona, Spain, 08026
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28009
    • Hgu Gregorio Maranon
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28223
    • Hospital Universitario Quirónsalud Madrid
  • Madrid, Spain, 28033
    • MD Anderson Cancer Centre Madrid
  • San Cristobal de La Laguna, Spain, 38320
    • Hospital Universitario de Canarias
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Sevilla, Spain, 41007
    • Hospital Universitario Virgen Macarena
• Sweden
  • Stockholm, Sweden, 14141
    • Karolinska University Hospital, Huddinge
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • London, United Kingdom, SE5 9RS
    • Northwick Park Hospital
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Nhs Foundation Trust - Chelsea
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates - Biltmore Cancer Center
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Los Angeles, California, United States, 90036
      • Synergy Hematology and Oncology Medical Associates
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare
    • Whittier, California, United States, 90603
      • American Institute of Research Corporate Office
  • Connecticut
    • Southington, Connecticut, United States, 06489
      • Cancer Center of Central Connecticut
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists & Research Institute
    • Spring Hill, Florida, United States, 34606
      • ASCLEPES Research Centers
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Clinical Trials of Swla Llc
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Saint Agnes Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Hospital
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic Hematology
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
    • Kansas City, Missouri, United States, 64132
      • Sarah Cannon Research Institute
  • New York
    • New Hyde Park, New York, United States, 11042
      • Clinical Research Alliance, Inc.
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health System
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates Pa
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Spring, Texas, United States, 77380
      • Renovatio Clinical Consultants Llc
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 years or older.
• Histologically confirmed, relapsed or refractory, follicular B-cell non-Hodgkin lymphoma (NHL) (follicular lymphoma) Grade 1, 2, and 3a.
• Ineligible for hematopoietic stem cell transplant.
• Must have been treated with at least 2 prior systemic therapies.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures > 1.5 cm in the longest dimension and ≥ 1.0 cm in the longest perpendicular dimension as assessed by computed tomography or magnetic resonance imaging.
• Must be willing to undergo an incisional, excisional, or core needle lymph node or tissue biopsy or provide a lymph node or tissue biopsy from the most recent available archival tissue.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Exclusion Criteria:

• Known histological transformation from indolent NHL to diffuse large B-cell lymphoma.
• 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.
• Prior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib).
• Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of study treatment administration.
• Active graft-versus-host 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Parsaclisib 20 mg QD for 8 Weeks Followed by 20 mg QW; Participants received parsaclisib 20 mg once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to approximately 52 weeks.	Drug: Parsaclisib; Parsaclisib tablets administered orally with water and without regard to food; Other Names: INCB050465
Experimental: Treatment B: Parsaclisib 20 mg QD for 8 Weeks Followed by 2.5 mg QD; Participants received parsaclisib 20 mg QD for 8 weeks followed by 2.5 mg QD for up to approximately 52 weeks.	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 With Parsaclisib Based on Lugano Classification Response 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),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 148 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate With Parsaclisib Based on Lugano Classification Response Criteria	CRR was defined as the percentage of participants with a CR as defined by revised 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 148 weeks
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 148 weeks
Progression-free Survival (PFS) With Parsaclisib	PFS was 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 148 weeks
Overall Survival (OS) With Parsaclisib	OS was defined as the time from the date of the first dose of study treatment until death from any cause.	Up to approximately 148 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 non-missing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement.	Up to approximately 148 weeks
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is defined as 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. TEAE is any AE either reported for first time or worsening of a pre-existing event after first dose of study drug and within 30 days of last administration of study drug regardless of starting new anti-lymphoma therapy. 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 148 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2018
• Primary Completion (Actual): February 26, 2021
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Follicular lymphoma; non-Hodgkin lymphoma (NHL); phosphatidylinositol 3-kinase (PI3K) δ inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular
• Other Study ID Numbers: INCB 50465-203 (CITADEL-203); Parsaclisib (Other Identifier: Incyte Corporation); 2017-001624-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• 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