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

NCT07104032 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: ONO-4059-172025-523389-26-00
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 14

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

Keywords

Bruton's tyrosine kinase (BTK)

Outcome Measures

Primary Outcomes (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.

  Estimated up to 24 months

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  Estimated up to 48 months]

• Overall Survival (OS)

  Estimated up to 48 months

• Complete Response Rate (CRR)

  Estimated up to 48 months

• Best Overall Response (BOR)

  Estimated up to 48 months]

• Time to Response (TTR)

  Estimated up to 48 months

Study Arms (2)

Tirabrutinib

EXPERIMENTAL

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

Drug: Tirabrutinib

Rituximab-Temozolomide (R-TMZ)

ACTIVE COMPARATOR

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; Drug: Temozolomide

Interventions

Tirabrutinib DRUG

Administered orally.

Also known as: ONO-4059

Tirabrutinib

Rituximab DRUG

Administered intravenously (IV).

Rituximab-Temozolomide (R-TMZ)

Temozolomide DRUG

Administered orally.

Rituximab-Temozolomide (R-TMZ)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathology report confirming the diagnosis of B-cell PCNSL
• 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.
• 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)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
• Adequate bone marrow, renal, and hepatic function per central lab values
• Participants must agree to comply with all defined contraceptive requirements

You may not qualify if:

• Participants with isolated intraocular PCNSL or spinal PCNSL with no brain lesions
• Participants with non-B-cell PCNSL
• Participants with systemic presence of lymphoma
• Refractory to temozolomide with or without rituximab-containing regimens in the last PCNSL treatment
• 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
• Active malignancy, other than PCNSL requiring systemic therapy
• Poorly controlled comorbidity, or history of medical conditions contraindicated per Investigator assessment
• Participants who are unable to swallow oral medication
• Prior Bruton's tyrosine kinase inhibitor treatment

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: collaborator
• Ono Pharmaceutical Co., Ltd.: lead

Study Sites (14)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

RECRUITING

HonorHealth Cancer Center

Scottsdale, Arizona, 85251, United States

RECRUITING

Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Providence Neurological Specialties West

Portland, Oregon, 97225, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

tirabrutinib; Rituximab; Temozolomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Team

  Deciphera Pharmaceuticals, LLC

  STUDY DIRECTOR

Central Study Contacts

Clinical Team

CONTACT

888-724-3274; clinicaltrials@deciphera.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)