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

Lymphoma Clinical Trial

— (CITADEL-205)  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03235544
• Other study ID #: INCB 50465-205 (CITADEL-205)
• Secondary ID: Parsaclisib2017-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 20, 2017
• Est. completion date: April 30, 2024

Study information

• Verified date: November 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 162
• Est. completion date: April 30, 2024
• Est. primary completion date: March 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (PI3Kd) 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).

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• Parsaclisib
Parsaclisib tablets administered orally with water and without regard to food.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Hopital de Jolimont	La Louviere
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni Nemocnice Kralovske Vinohadry, Interni Hematologicka Klinika	Prague
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Prague 10
Czechia	Charles University General Hospital	Prague 2
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus Universitets Hospital	Aarhus
Denmark	Odense Universitetshospital (Ouh) (Odense University Hospital)	Odense C
Denmark	Zealand University Hospital	Roskilde
France	Avicenne Hospital	Bobigny
France	Chu de Clermont - Ferrand- Hospital Estaing	Clermont-ferrand
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	University Hospital Grenoble	Grenoble
France	Centre Hospitalier Departemental - La-Roche-Sur-Yon - Les Oudairies	La Roche Sur Yon
France	Centre Hospitalier Universitaire de Grenoble	La Tronche
France	Centre Hospitalier de Versailles	Le Chesnay
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Lyon
France	Centre Antoine Lacassagne	Nice
France	H?Pital Universitaire Piti?-Salp?Tri?Re	Paris
France	Hopital Saint-Louis	Paris
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite Cedex
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
France	Centre Henri Becquerel	Rouen
France	Chru Hopitaux de Tours, Hospital Bretonneau	Tours
France	Institute Gustave Roussy (Igr)	Villejuif Cedex
Germany	Praxis Brudler, Heinrich, Bangerter	Augsburg
Germany	Universit?Tsklinikum Essen	Essen
Germany	Universitaetsklinikum Essen	Essen
Germany	Justus-Liebig University	Giessen
Germany	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz
Germany	Kliniken Maria Hilf	Moenchengladbach
Germany	Rotkreuzklinikum Munich	Munchen
Germany	Universit?Tsklinikum Ulm	ULM
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Hebrew University Medical Center	Jerusalem
Israel	Hadassah Hebrew University Medical Center Ein Karem Hadassah	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Petach Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Centro Ricerche Cliniche	Bologna
Italy	Azienda Policlinico Vittorio Emanuele	Catania
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milano	MI
Italy	Grande Ospedale Metropolitano Niguarda	Milano
Italy	Ospedale Niguarda Ca Granda	Milano
Italy	A.O.U. Di Modena - Policlinico	Modena
Italy	A.O.U. Federico Ii	Napoli
Italy	Aou Maggiore Della Carita	Novara
Italy	Ospedali Riuniti Villa Sofia Cervello	Palermo
Italy	Sapienza University	Rome
Italy	Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte	Siena
Italy	Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza	Torino
Poland	Beskidzkie Centrum Onkologii Im.Jana Pawla Ii	Bielsko-biala
Poland	Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza	Brzozow
Poland	University Clinical Center	Gdansk
Poland	Pratia McM Krakow	Krakow
Poland	Nu-Med Centrum Diagnostykii I Terapii Onkologicznej	Tomaszow Mazowiecki
Poland	Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie	Warszawa
Spain	Hospital Del Mar	Barcelona
Spain	Hospital General Universitari Vall D Hebron	Barcelona
Spain	Hospital Universitari Mutua Terrassa	Barcelona
Spain	Institut Catala D Oncologia	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Paz	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Md Anderson Cancer Centre Madrid	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Universitario Y Politecnic La Fe	Valencia
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	University College London Hospitals (Uclh)	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Rocky Mountain Cancer Center-Aurora	Aurora	Colorado
United States	Texas Oncology	Austin	Texas
United States	University of Alabama At Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Asclepes Research Centers	Brooksville	Florida
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Willamette Valley Cancer Institute	Eugene	Oregon
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Hattiesburg Clinic Hematology	Hattiesburg	Mississippi
United States	Loyola University Medical Center	Maywood	Illinois
United States	Clinical Research Alliance, Inc.	New Hyde Park	New York
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Kaiser Permanente - Northwest	Portland	Oregon
United States	Texas Oncology San Antonio	San Antonio	Texas
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	Renovatio Clinical	The Woodlands	Texas
United States	Texas Oncology - Tyler	Tyler	Texas
United States	Bond & Steele Clinic, P.A.	Winter Haven	Florida
United States	Yakima Valley Memorial Hospital/North Star	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Denmark,  France,  Germany,  Israel,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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