Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study)
- Conditions
- Primary CNS LymphomaRefractory Primary Central Nervous System Lymphoma
- Interventions
- Registration Number
- NCT04947319
- Lead Sponsor
- Ono Pharmaceutical Co. Ltd
- Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 112
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2) Tirabrutinib Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + rituximab/methotrexate/procarbazine/vincristine (R-MPV) Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A) Tirabrutinib Patients with relapsed or refractory PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib monotherapy. Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1) Tirabrutinib Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + methotrexate/temozolomide/rituximab (MTR)
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) (Part A) 1 year Overall response rate is defined as the proportion of patients with a best overall response of Complete response (CR), Complete response - unconfirmed (CRu), or (=partial response (PR) as determined by an independent review committee according to the International PCNSL Collaborative Group (IPCG) criteria.
Tirabrutinib dose estimate (Part B) 1 month Estimate of tirabrutinib dose in combination with each backbone induction regimen (MTR and R-MPV) based upon treatment related AEs, SAEs, and toxicities observed during the initial cycle of induction therapy in the dose-ranging phase
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during induction (Part B) 4 months Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
Complete response rate (CRR) (Part B) 4 months Complete response rate is defined as the proportion of patients with a best overall response of CR or CRu as determined by an independent review committee according to the IPCG criteria.
- Secondary Outcome Measures
Name Time Method Time to response (TTR) (Part A and B) 1 year Time to response is defined as the time between the date of first administration of tirabrutinib and the date of first response (CR, CRu, or PR) as determined by IRC according to the IPCG criteria.
PK parameters (Tmax) of tirabrutinib in the plasma (Part A and B) 29 days Best overall response (BOR) (Part A and B) 1 year Best overall response based on independent review committee (IRC) response determination is defined as the best response and is derived programmatically based upon the visit responses determined by IRC from the date of administration of tirabrutinib to the date of PD as determined by IRC or the date of initiation of subsequent anticancer therapy for PCNSL, whichever occurs first.
Change in corticosteroid dose (Part A) 2 years Descriptive statistics will be calculated for the actual corticosteroid dose and the change from baseline at each assessment point.
PK parameters (AUC) of tirabrutinib in the plasma (Part A and B) 29 days Duration of response (DOR) (Part A and B) 2 years Duration of response is defined as the time between the date of first response (CR, CRu, or PR) and the date of the first PD according to the IPCG criteria, or date of death due to any cause, whichever occurs first.
Incidence and severity of AEs and SAEs (Part A and B) 2 years Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
Laboratory abnormality profile of tirabrutinib as measured by incidence and severity of clinical laboratory abnormalities (Part A and B) 2 years Results of laboratory tests
PK parameters (Cmax) of tirabrutinib in the plasma (Part A and B) 29 days ECG parameters by 12 lead ECG (Part A and B) 2 years Heart rate, RR and QT intervals, QTc (QTcF, QTcB), PR interval, and QRS width.
Trial Locations
- Locations (45)
University of Alabama at Birmingham School of Medicine
🇺🇸Birmingham, Alabama, United States
Mayo Clinic- Phoenix
🇺🇸Phoenix, Arizona, United States
City of Hope Comprehensive Breast Cancer Center
🇺🇸Duarte, California, United States
Cedar Sinai Medical Cancer
🇺🇸Hollywood, California, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Georgetown University, Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
Mayo Clinic- Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Miami-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Orlando Health
🇺🇸Orlando, Florida, United States
Moffitt Cancer Center- Miami
🇺🇸Pembroke Pines, Florida, United States
Piedmont Healthcare
🇺🇸Atlanta, Georgia, United States
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Norton Cancer Institute - St. Matthews
🇺🇸Louisville, Kentucky, United States
Maine Medical Partners Neurology (Maine Neurology)
🇺🇸Scarborough, Maine, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute - Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
University Of Michigan
🇺🇸Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Mayo Clinic- Rochester
🇺🇸Rochester, Minnesota, United States
The University of Kansas Cancer Center (KUCC) (Kansas City Cancer Center (KCCC)) - North
🇺🇸Kansas City, Missouri, United States
Hackensack University Medical Center - John Theurer Cancer
🇺🇸Hackensack, New Jersey, United States
Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
Columbia University Irving Medical Center
🇺🇸New York, New York, United States
Levine Cancer Center
🇺🇸Charlotte, North Carolina, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Providence Health Cancer Center
🇺🇸Portland, Oregon, United States
Penn State Hershey Cancer Center
🇺🇸Hershey, Pennsylvania, United States
Abramson Cancer Center University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Hillman Cancer Center, University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Lifespan Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
University of Tennessee Cancer Institute
🇺🇸Knoxville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Houston Methodist Research Institute (HMRI)
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The University of Utah - Huntsman Cancer Institute (HCI)
🇺🇸Salt Lake City, Utah, United States
The University of Vermont - Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States