A Study of INCB050465 in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a Bruton's Tyrosine Kinase (BTK) Inhibitor
- Registration Number
- NCT03235544
- Lead Sponsor
- Incyte Corporation
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 162
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: Treatment B (Exposed to Ibrutinib) Parsaclisib 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. Cohort 1: Treatment A (Exposed to Ibrutinib) Parsaclisib 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. Cohort 2: Treatment B (Bruton's Tyrosine Kinase Inhibitor Naïve) Parsaclisib 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. Cohort 2: Treatment A (Bruton's Tyrosine Kinase Inhibitor Naïve) Parsaclisib 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to 1016 days 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Up to 1016 days 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.
Complete Response Rate (CRR) Up to 1016 days 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.
Progression-Free Survival (PFS) Up to 1016 days 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.
Overall Survival (OS) Up to 2017 days OS is defined as the time from the date of the first dose of study treatment until death from any cause.
Best Percent Change From Baseline in Target Lesion Size Up to 1016 days 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.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) From first dose of study drug up to 2045 days 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.
Trial Locations
- Locations (103)
Justus-Liebig University
🇩🇪Giessen, Germany
A.O.U. Di Modena - Policlinico
🇮🇹Modena, Italy
University Clinical Center
🇵🇱Gdansk, Poland
Hospital Universitari Mutua Terrassa
🇪🇸Barcelona, Spain
Hospital General Universitari Vall D Hebron
🇪🇸Barcelona, Spain
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Hattiesburg Clinic Hematology
🇺🇸Hattiesburg, Mississippi, United States
Oncology Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
Yakima Valley Memorial Hospital/North Star
🇺🇸Yakima, Washington, United States
Universitair Ziekenhuis Gent
🇧🇪Gent, Oost-Vlaanderen, Belgium
Centre Hospitalier Lyon-Sud
🇫🇷Pierre-Bénite Cedex, France
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Rotkreuzklinikum Munich
🇩🇪Munchen, Germany
Ospedale Niguarda Ca Granda
🇮🇹Milano, Italy
A.O.U. Federico Ii
🇮🇹Napoli, Italy
Fondazione Irccs Istituto Nazionale Dei Tumori
🇮🇹Milano, MI, Italy
Aou Maggiore Della Carita
🇮🇹Novara, Italy
Sapienza University
🇮🇹Rome, Italy
H�Pital Universitaire Piti�-Salp�Tri�Re
🇫🇷Paris, France
Institut Jules Bordet
🇧🇪Brussels, Belgium
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
🇩🇪Mainz, Germany
Rambam Medical Center
🇮🇱Haifa, Israel
Hadassah Hebrew University Medical Center
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Willamette Valley Cancer Institute
🇺🇸Eugene, Oregon, United States
University Hospital Grenoble
🇫🇷Grenoble, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Institute Gustave Roussy (Igr)
🇫🇷Villejuif Cedex, France
Kliniken Maria Hilf
🇩🇪Moenchengladbach, Germany
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria Alle Scotte
🇮🇹Siena, Italy
Centrum Onkologii-Instytut Im. Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
University of Alabama At Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Kaiser Permanente - Northwest
🇺🇸Portland, Oregon, United States
Texas Oncology San Antonio
🇺🇸San Antonio, Texas, United States
Rocky Mountain Cancer Center-Aurora
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Asclepes Research Centers
🇺🇸Brooksville, Florida, United States
St. Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Bond & Steele Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
Clinical Research Alliance, Inc.
🇺🇸New Hyde Park, New York, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Hopital de Jolimont
🇧🇪La Louviere, Belgium
Zealand University Hospital
🇩🇰Roskilde, Denmark
Fakultni Nemocnice Kralovske Vinohrady
🇨🇿Prague 10, Czechia
Universitaire Ziekenhuis Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Fakultni Nemocnice Kralovske Vinohadry, Interni Hematologicka Klinika
🇨🇿Prague, Czechia
Fakultni Nemocnice Hradec Kralove
🇨🇿Hradec Kralove, Czechia
Charles University General Hospital
🇨🇿Prague 2, Czechia
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Odense Universitetshospital (Ouh) (Odense University Hospital)
🇩🇰Odense C, Denmark
Aarhus Universitets Hospital
🇩🇰Aarhus, Denmark
Avicenne Hospital
🇫🇷Bobigny, France
Centre Hospitalier Universitaire Henri Mondor
🇫🇷Creteil, France
Chu de Clermont - Ferrand- Hospital Estaing
🇫🇷Clermont-ferrand, 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
Hopital Saint-Louis
🇫🇷Paris, France
Centre Henri Becquerel
🇫🇷Rouen, France
Chru Hopitaux de Tours, Hospital Bretonneau
🇫🇷Tours, France
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Praxis Brudler, Heinrich, Bangerter
🇩🇪Augsburg, Germany
Universit�Tsklinikum Essen
🇩🇪Essen, Germany
Universit�Tsklinikum Ulm
🇩🇪ULM, Germany
Hadassah Hebrew University Medical Center Ein Karem Hadassah
🇮🇱Jerusalem, Israel
Rabin Medical Center - Beilinson Hospital
🇮🇱Petach Tikva, Israel
Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Italy
Azienda Policlinico Vittorio Emanuele
🇮🇹Catania, Italy
Centro Ricerche Cliniche
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza
🇮🇹Torino, Italy
Ospedali Riuniti Villa Sofia Cervello
🇮🇹Palermo, Italy
Beskidzkie Centrum Onkologii Im.Jana Pawla Ii
🇵🇱Bielsko-biala, Poland
Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza
🇵🇱Brzozow, Poland
Hospital Del Mar
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Pratia McM Krakow
🇵🇱Krakow, Poland
Nu-Med Centrum Diagnostykii I Terapii Onkologicznej
🇵🇱Tomaszow Mazowiecki, Poland
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Institut Catala D Oncologia
🇪🇸Barcelona, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Md Anderson Cancer Centre Madrid
🇪🇸Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de La Paz
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain
Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Hospital Universitario Y Politecnic La Fe
🇪🇸Valencia, Spain
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
University College London Hospitals (Uclh)
🇬🇧London, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Texas Oncology
🇺🇸Austin, Texas, United States