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NCT07104032PHASE3Recruiting

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

Ono Pharmaceutical Co., Ltd.

Start Date

6/12/2026

Completion Date

12/1/2029

Summary

The purpose of this clinical trial is to evaluate efficacy and safety of tirabrutinib alone compared with rituximab and temozolomide (R-TMZ) combination therapy in participants with Relapsed/Refractory Primary Central Nervous System Lymphoma (PCNSL).

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Tirabrutinib

DRUG

Rituximab

DRUG

Temozolomide

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Conditions

Relapsed/Refractory Primary Central Nervous System Lymphoma

Locations

Mayo Clinic Cancer Center

Phoenix, Arizona 85054

United States

HonorHealth Cancer Center

Scottsdale, Arizona 85251

United States

Providence Medical Foundation

Fullerton, California 92835

United States

UC Irvine Health

Orange, California 92868

United States

Yale Cancer Center

New Haven, Connecticut 06520

United States

John Hopkins University

Washington D.C., District of Columbia 20016

United States

University of Florida Gainesville

Gainesville, Florida 32610

United States

Mayo Clinic Cancer Center

Jacksonville, Florida 32224

United States

University of Maryland

Baltimore, Maryland 21201

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02115

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02115

United States

Mayo Clinic Cancer Center

Rochester, Minnesota 55905

United States

Hackensack University Medical Center

Hackensack, New Jersey 07601

United States

Atlantic Health Overlook Medical Center

Summit, New Jersey 07901

United States

NYU Langone Health

New York, New York 10016

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Providence Neurological Specialties West

Portland, Oregon 97225

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

University Hospital Ostrava

Ostrava, Czechia 708 52

Czechia

Hôpitaux de Marseille

Marseille, France 13005

France

Hospital Center University De Montpellier

Montpellier, France 34090

France

ASST Spedali Civili di Brescia

Brescia, Italy 25123

Italy

Hospital Clínic de Barcelona

Barcelona, Spain

Spain