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

NCT ID: NCT07104032

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2029-12-31

Brief 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).

Conditions

Relapsed/Refractory Primary Central Nervous System Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tirabrutinib

Tirabrutinib 480 milligram (mg) orally every day (QD), as monotherapy in 28-day cycles.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

Administered intravenously (IV).

Temozolomide

Intervention Type: DRUG

Administered orally.

Interventions

Tirabrutinib

Administered orally.

Intervention Type: DRUG

Rituximab

Administered intravenously (IV).

Intervention Type: DRUG

Temozolomide

Administered orally.

Intervention Type: DRUG

Other Intervention Names

ONO-4059

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deciphera Pharmaceuticals, LLC

INDUSTRY

Sponsor Role: collaborator

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Team

Role: STUDY_DIRECTOR

Deciphera Pharmaceuticals, LLC

Central Contacts

Clinical Team

Role: CONTACT

clinicaltrials@deciphera.com

888-724-3274

Other Identifiers

ONO-4059-17

Identifier Type: -

Identifier Source: org_study_id