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

Ono Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Relapsed/Refractory Primary Central Nervous System Lymphoma

Treatments: Drug: Temozolomide; Drug: Tirabrutinib; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07104032

ONO-4059-17

Details and patient eligibility

About

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).

Enrollment: 132 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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132 participants in 2 patient groups

Tirabrutinib

Experimental group

Description:

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

Treatment:

Drug: Tirabrutinib

Rituximab-Temozolomide (R-TMZ)

Active Comparator group

Description:

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.

Treatment:

Drug: Rituximab

Drug: Temozolomide