IGNITE: Study of Tirabrutinib vs Rituximab/Temozolomide for Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by Ono Pharmaceutical Co., Ltd.
Sponsor
Ono Pharmaceutical Co., Ltd.
Information Provided by (Responsible Party)
Ono Pharmaceutical Co., Ltd.
Clinicaltrials.gov Identifier
NCT07104032
Other Study ID Numbers:
ONO-4059-17
First Submitted
July 28, 2025
First Posted
August 4, 2025
Last Update Posted
August 17, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Relapsed/Refractory Primary Central Nervous System Lymphoma
Drug: TirabrutinibDrug: Rituximab

Study Design

Study TypeInterventional
Actual Enrollment132 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 3, Multi-regional, Open-label, Randomized Study of Tirabrutinib vs Rituximab and Temozolomide in Participants With Relapsed/Refractory Primary Central Nervous System Lymphoma
Study Start DateJune 11, 2026
Actual Primary Completion Date1yr 3mos from now
Actual Study Completion Date3yrs 3mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Tirabrutinib
Tirabrutinib 480 milligram (mg) orally every day (QD), as monotherapy in 28-day cycles.
Drug: Tirabrutinib
Administered orally.
Rituximab-Temozolomide (R-TMZ)
Rituximab 375 milligram per square meter (mg/m2) intravenously (IV) and temozolomide 150 mg/m2/day orally, as combination therapy for Cycle 1 through 6.
Drug: Rituximab
Administered intravenously (IV).

Outcome Measures

Primary Outcome Measures
  1. Progression Free Survival (PFS)
    PFS based on blinded Independent Review Committee (BIRC) assessment according to International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) criteria, defined as time from randomization to progressive disease (PD) or death due to any cause, whichever occurs first.
Secondary Outcome Measures
  1. Overall Response Rate (ORR)
    ORR based on BIRC per IPCG criteria, defined as the percentage of participants with a best overall response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR).
  2. Overall Survival (OS)
    OS defined as time from randomization until death due to any cause.
  3. Complete Response Rate (CRR)
    CRR based on BIRC per IPCG criteria, defined as the percentage of participants with a best overall response of CR or CRu.
  4. Best Overall Response (BOR)
    BOR based on BIRC per IPCG criteria, defined as the best response from randomization to the date of PD or the date of initiation of subsequent anticancer therapy for PCNSL, whichever occurs first.
  5. Time to Response (TTR)
    TTR based on BIRC per IPCG criteria, defined as time between randomization and the date of first response of CR, CRu, or PR.
  6. Time to Complete Response (TTCR)
    TTCR based on BIRC per IPCG criteria, defined as the time between randomization and the date of first complete response (CR or CRu).
  7. Duration of Response (DOR)
    DOR based on BIRC per IPCG criteria, defined as the time between the date of first response (CR, CRu, or PR) and the date of the first PD or date of death due to any cause, whichever occurs first.
  8. Disease Free Survival (DFS)
    DFS based on BIRC per IPCG criteria, defined as the time between the date of first complete response (CR or CRu) and the date of the first PD, or date of death due to any cause, whichever occurs first.
  9. Change from Baseline in Corticosteroid Dose

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Inclusion Criteria 1. Pathology report confirming the diagnosis of B-cell PCNSL 2. Relapsed or refractory B-cell PCNSL with at least 1 prior high-dose methotrexate (HD-MTX) based therapy for PCNSL:
Relapsed disease: Participants who achieved a response (CR, CRu, PR) to the last treatment and subsequently experienced disease progression.
Refractory disease: Participants whose best response to the last treatment was stable disease or PD. 3. One or more bi-dimensionally measurable brain lesions with a minimum diameter greater than or equal to (≥)1 centimeter (cm) × ≥1 cm in gadolinium-enhanced magnetic resonance imaging (MRI) 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 5. Adequate bone marrow, renal, and hepatic function per central lab values 6. Participants must agree to comply with all defined contraceptive requirements
Exclusion Criteria
Inclusion Criteria 1. Pathology report confirming the diagnosis of B-cell PCNSL 2. Relapsed or refractory B-cell PCNSL with at least 1 prior high-dose methotrexate (HD-MTX) based therapy for PCNSL:
Relapsed disease: Participants who achieved a response (CR, CRu, PR) to the last treatment and subsequently experienced disease progression.
Refractory disease: Participants whose best response to the last treatment was stable disease or PD. 3. One or more bi-dimensionally measurable brain lesions with a minimum diameter greater than or equal to (≥)1 centimeter (cm) × ≥1 cm in gadolinium-enhanced magnetic resonance imaging (MRI) 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 5. Adequate bone marrow, renal, and hepatic function per central lab values 6. Participants must agree to comply with all defined contraceptive requirements Exclusion Criteria 1. Participants with isolated intraocular PCNSL or spinal PCNSL with no brain lesions 2. Participants with non-B-cell PCNSL 3. Participants with systemic presence of lymphoma 4. Refractory to temozolomide with or without rituximab-containing regimens in the last PCNSL treatment 5. Concomitant systemic corticosteroid exposure within 14 days before starting study drug per Investigator assessment with the exception of the following:
Equivalent of up to 10 milligram per day (mg/day) of prednisone for a disease other than PCNSL
Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day dexamethasone) for participants with lesions of the brain and/or spinal cord 6. Active malignancy, other than PCNSL requiring systemic therapy 7. Poorly controlled comorbidity, or history of medical conditions contraindicated per Investigator assessment 8. Participants who are unable to swallow oral medication 9. Prior Bruton's tyrosine kinase inhibitor treatment

Contacts and Locations

Sponsors and CollaboratorsOno Pharmaceutical Co., Ltd.
Locations
Mayo Clinic Cancer Center | Phoenix Arizona, United States, 85054HonorHealth Cancer Center | Scottsdale Arizona, United States, 85251Providence Medical Foundation | Fullerton California, United States, 92835UC Irvine Health | Orange California, United States, 92868Yale Cancer Center | New Haven Connecticut, United States, 06520John Hopkins University | Washington D.C. District of Columbia, United States, 20016University of Florida Gainesville | Gainesville Florida, United States, 32610Mayo Clinic Cancer Center | Jacksonville Florida, United States, 32224University of Maryland | Baltimore Maryland, United States, 21201Massachusetts General Hospital | Boston Massachusetts, United States, 02114Beth Israel Deaconess Medical Center | Boston Massachusetts, United States, 02115Dana-Farber Cancer Institute | Boston Massachusetts, United States, 02115Mayo Clinic Cancer Center | Rochester Minnesota, United States, 55905Hackensack University Medical Center | Hackensack New Jersey, United States, 07601Atlantic Health Overlook Medical Center | Summit New Jersey, United States, 07901NYU Langone Health | New York New York, United States, 10016Columbia University Irving Medical Center | New York New York, United States, 10032Memorial Sloan Kettering Cancer Center | New York New York, United States, 10065Duke University Medical Center | Durham North Carolina, United States, 27710Providence Neurological Specialties West | Portland Oregon, United States, 97225Penn State Health Milton S Hershey Medical Center | Hershey Pennsylvania, United States, 17033UPMC Hillman Cancer Center | Pittsburgh Pennsylvania, United States, 15232Rhode Island Hospital | Providence Rhode Island, United States, 02903Epworth Healthcare | Melbourne Victoria, Australia, 3002University Hospital Ostrava | Ostrava Czechia, Czechia, 708 52University Hospital Královské Vinohrady | Prague Czechia, Czechia, 10034Hôpitaux de Marseille | Marseille France, France, 13005Hospital Center University De Montpellier | Montpellier France, France, 34090ASST Spedali Civili di Brescia | Brescia Italy, Italy, 25123IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST | Meldola Italy, Italy, 47014Hospital Clínic de Barcelona | Barcelona Spain, Spain, Hospital Universitario 12 De Octubre | Madrid Spain, Spain, 28041
Investigators
Study Director: Clinical Team, Deciphera Pharmaceuticals, LLC