An Open-label Phase II Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Tirabrutinib in Patients With Primary Central Nervous System Lymphoma (PCNSL)
Overview
- Phase
- Phase 2
- Intervention
- Tirabrutinib
- Conditions
- Refractory Primary Central Nervous System Lymphoma
- Sponsor
- Ono Pharmaceutical Co. Ltd
- Enrollment
- 119
- Locations
- 39
- Primary Endpoint
- Overall response rate (ORR) (Part A)
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A)
Patients with relapsed or refractory PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib monotherapy.
Intervention: Tirabrutinib
Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1)
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + methotrexate/temozolomide/rituximab (MTR)
Intervention: Tirabrutinib
Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2)
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + rituximab/methotrexate/procarbazine/vincristine (R-MPV)
Intervention: Tirabrutinib
Outcomes
Primary Outcomes
Overall response rate (ORR) (Part A)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- Time to response (TTR) (Part A and B)(1 year)
- PK parameters (Tmax) of tirabrutinib in the plasma (Part A and B)(29 days)
- Best overall response (BOR) (Part A and B)(1 year)
- Change in corticosteroid dose (Part A)(2 years)
- PK parameters (AUC) of tirabrutinib in the plasma (Part A and B)(29 days)
- Duration of response (DOR) (Part A and B)(2 years)
- Incidence and severity of AEs and SAEs (Part A and B)(2 years)
- Laboratory abnormality profile of tirabrutinib as measured by incidence and severity of clinical laboratory abnormalities (Part A and B)(2 years)
- 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)