Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study)

Phase 2

Recruiting

• Conditions: Primary CNS Lymphoma; Refractory Primary Central Nervous System Lymphoma
• Interventions: Drug: Tirabrutinib

• 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

Study Timeline

• Study First Submitted: 2021-06-16
• Study First Submitted QC: 2021-06-23
• Study First Posted: 2021-07-01
• Study Start: 2021-12-29
• Status Verified: 2025-05
• Last Update Submitted: 2025-06-01
• Last Update Posted: 2025-06-03
• Primary Completion: 2027-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

Not provided

Exclusion Criteria

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

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