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

Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03144674
• Other study ID #: INCB 50465-204 (CITADEL-204)
• Secondary ID: Parsaclisib
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: May 31, 2024

Study information

• Verified date: February 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: May 31, 2024
• Est. primary completion date: January 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone

Intervention

Drug:
• Parsaclisib
Parsaclisib at the protocol-defined dose.

Locations

Country	Name	City	State
Argentina	Aou Maggiore Della Carita	Rosario
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Icon Cancer Care	Auchenflower	Queensland
Australia	Calvary North Adelaide Hospital	North Adelaide	South Australia
Belgium	Cliniques Universitaires Ucl Saint-Luc	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Denmark	Aalborg University Hospital	Aalborg
Denmark	Zealand University Hospital	Roskilde
France	Avicenne Hospital	Bobigny
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Chu Limoges - Hospital Le Cluzeau	Limoges Cedex
France	H?Pital Universitaire Piti?-Salp?Tri?Re	Paris
France	Hopital Saint-Louis	Paris
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud	Pierre-benite
France	Centre Henri Becquerel	Rouen
France	Institute Gustave Roussy (Igr)	Villejuif
Germany	Universit?Tsklinikum Essen	Essen
Germany	Universitatsmedizin Gottingen	Gottingen
Germany	Universit?Tsklinikum Schleswig-Holstein	Kiel
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz
Germany	Universit?Tsklinikum Ulm	ULM
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Hebrew University Medical Center Ein Karem Hadassah	Jerusalem
Israel	Rabin Medical Center - Beilinson Hospital	Petach Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	University of Bologna, Institute of Haematology ?L. E A. Ser?Gnoli?	Bologna
Italy	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori	Meldola
Italy	Fondazione Centro San Raffaele - Milano	Milano
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milano
Italy	Azienda Ospedaliera San Gerardo Di Monza	Monza
Italy	Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cervello"	Palermo
Italy	Presidio Ospedaliero Pescara	Pescara
Italy	Ospedale Delle Croci - Ematologia Ravenna	Ravenna
Italy	Sapienza University	Rome
Poland	Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie	Gdansk
Poland	Szpitale Wojew?Dzkie W Gdyni Sp??Ka Z Ograniczon? Odpowiedzialno?Ci?	Gdansk
Poland	Malopolskie Centrum Medyczne S.C.	Krakow
Poland	Klinika Transplantacji Komorel Krwiotworczych	Warsaw
Poland	Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie	Warszawa
Spain	Hospital General Universitari Vall D Hebron	Barcelona
Spain	Ico Institut Catala D Oncologia	Barcelona
Spain	Hgu Gregorio Maranon	Madrid
Spain	Hospital Universitario Hm Sanchinarro	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Universitario de Salamanca	Salamanca
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Kent Oncology Centre - Maidstone Hospital	Maidstone
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	University of Southampton	Southampton
United States	University of Michigan Cancer Center	Ann Arbor	Michigan
United States	University of Alabama At Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Gabrail Cancer Center	Canton	Ohio
United States	Charleston Hematology Oncology Associates Pa	Charleston	South Carolina
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Rush University Medical Center - Consultants in Hematology	Chicago	Illinois
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Valley View Hospital	Glenwood Springs	Colorado
United States	St. Mary'S Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Saint Luke'S Hospital of Kansas City	Kansas City	Missouri
United States	Clinical Trials of Swla Llc	Lake Charles	Louisiana
United States	COMPREHENSIVE CANCER CeNTERS OF NEVADA - TWAIN	Las Vegas	Nevada
United States	Advanced Pharma Cr	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Clinical Research Alliance	New Hyde Park	New York
United States	Nyu Cancer Institute	New York	New York
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Boca Raton Clinical Research Medical Inc.	Plantation	Florida
United States	Torrance Health Association	Redondo Beach	California
United States	Sansum Clinic	Santa Barbara	California
United States	Central Coast Medical Oncology	Santa Maria	California
United States	UCLA Healthcare Hematology-Oncology	Santa Monica	California
United States	St. Joseph Heritage Healthcare	Santa Rosa	California
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	Arizona Oncology Associates	Tempe	Arizona
United States	Renovatio Clinical	The Woodlands	Texas
United States	Asclepes Research Centers	Weeki Wachee	Florida
United States	White Plains Hospital	White Plains	New York
United States	Innovative Clinical Research Institute	Whittier	California
United States	Loyola University Medical Center	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 161 weeks
Secondary	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 approximately 161 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 161 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 161 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 161 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 161 weeks