Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study)

NCT04947319 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ONO-4059-09
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 39

Brief Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)

Conditions

Refractory Primary Central Nervous System Lymphoma; Primary CNS Lymphoma

Keywords

Bruton's Tyrosine Kinase Inhibitor, BTKi, tirabrutinib, ONO-4059, PROSPECT

Outcome Measures

Primary Outcomes (4)

• Overall response rate (ORR) (Part A)

  Overall response rate is defined as the proportion of patients with a best overall response of Complete response (CR), Complete response - unconfirmed (CRu), or (=partial response (PR) as determined by an independent review committee according to the International PCNSL Collaborative Group (IPCG) criteria.

  1 year

• Tirabrutinib dose estimate (Part B)

  Estimate of tirabrutinib dose in combination with each backbone induction regimen (MTR and R-MPV) based upon treatment related AEs, SAEs, and toxicities observed during the initial cycle of induction therapy in the dose-ranging phase

  1 month

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during induction (Part B)

  Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.

  4 months

• Complete response rate (CRR) (Part B)

  Complete response rate is defined as the proportion of patients with a best overall response of CR or CRu as determined by an independent review committee according to the IPCG criteria.

  4 months

Secondary Outcomes (10)

• Duration of response (DOR) (Part A and B)

  2 years

• Time to response (TTR) (Part A and B)

  1 year

• Best overall response (BOR) (Part A and B)

  1 year

• Change in corticosteroid dose (Part A)

  2 years

• Incidence and severity of AEs and SAEs (Part A and B)

  2 years

Study Arms (3)

Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A)

EXPERIMENTAL

Patients with relapsed or refractory PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib monotherapy.

Drug: Tirabrutinib

Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1)

EXPERIMENTAL

Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + methotrexate/temozolomide/rituximab (MTR)

Drug: Tirabrutinib

Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2)

EXPERIMENTAL

Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + rituximab/methotrexate/procarbazine/vincristine (R-MPV)

Drug: Tirabrutinib

Interventions

Tirabrutinib DRUG

Part A: Tirabrutinib 480 mg, taken orally, once a day on an empty stomach. Tirabrutinib treatment may be continued until disease progression or clinically unacceptable toxicity is observed.

Also known as: ONO-4059

Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A)

Eligibility Criteria

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

You may qualify if:

• Written informed consent by the patient prior to screening
• Patients aged ≥ 18 years on the day of consenting to the study
• Pathologic diagnosis of PCNSL
• Relapse or refractory PCNSL with at least one prior high dose methotrexate (HD-MTX) based therapy for PCNSL
• Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced magnetic resonance imaging (MRI) performed within 14 days before starting tirabrutinib treatment
• Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1 or 2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal, and hepatic function
• Written informed consent by the patient prior to screening
• Patients aged ≥ 18 years on the day of consenting to the study
• Pathologic diagnosis of PCNSL within the past 3 months
• No prior anti-tumor treatments for PCNSL
• Patients who, in the opinion of the Investigator, are suitable to receive treatment with a high dose methotrexate containing regimen
• Measurable brain lesion with a minimum diameter \> 1.0 cm in gadolinium enhanced MRI performed within 14 days before starting study treatment
• ECOG PS of 0, 1 or 2

You may not qualify if:

• Intraocular PCNSL with no brain lesion
• Patient who is intolerant of contrast enhanced MRI due to allergic reactions to contrast agents
• Patient with non-B cell PCNSL
• Patient with systemic presence of lymphoma
• Prior chemotherapy within 21 days, nitrosourea within 42 days, an antibody drug with anticancer activity (e.g., rituximab) within 28 days, prior radiotherapy within 14 days, prior major invasive surgery within 28 days, or allogeneic stem cell transplant within 6 months before starting tirabrutinib treatment
• Prior BTK inhibitor treatment
• Prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, before starting tirabrutinib treatment
• Concomitant systemic corticosteroid on an ongoing basis within 14 days before starting tirabrutinib treatment, with the exception of the following:
• Equivalent of up to 10 mg/day of prednisone for a disease other than PCNSL
• Equivalent of up to 50 mg/day of prednisone (equal to 8 mg/day of dexamethasone) for patients with lesions of the brain or spinal cord or both
• Patient who has received a CYP3A4 inducer or P-gp inducer within 14 days before starting tirabrutinib treatment
• Concomitant warfarin, any other warfarin derivative anticoagulant, vitamin K antagonists, novel oral anticoagulants, or antiplatelet therapy on an ongoing basis within 7 days before starting tirabrutinib treatment
• Active malignancy, other than PCNSL requiring systemic therapy
• Poorly controlled comorbidity, severe heart, severe lung disease, clinically significant liver diseases that could affect protocol compliance or safety or efficacy assessments
• Patient with bleeding diathesis

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (39)

University of Alabama at Birmingham School of Medicine

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic- Phoenix

Phoenix, Arizona, 85054, United States

Location

City of Hope Comprehensive Breast Cancer Center

Duarte, California, 91010, United States

Location

University of California, Irvine

Irvine, California, 92868, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Georgetown University, Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

Mayo Clinic- Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Moffitt Cancer Center- Miami

Pembroke Pines, Florida, 33028, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30318, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute - Brigham & Women's Hospital

Boston, Massachusetts, 02215, United States

Location

University Of Michigan

Ann Arbor, Michigan, 41809, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

The University of Kansas Cancer Center (KUCC) (Kansas City Cancer Center (KCCC)) - North

Kansas City, Missouri, 64154, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center - John Theurer Cancer

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering

New York, New York, 10022, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Providence Health Cancer Center

Portland, Oregon, 97239, United States

Location

Penn State Hershey Cancer Center

Hershey, Pennsylvania, 17033, United States

Location

Abramson Cancer Center University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hillman Cancer Center, University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Lifespan Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Houston Methodist Research Institute (HMRI)

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The University of Utah - Huntsman Cancer Institute (HCI)

Salt Lake City, Utah, 84112, United States

Location

The University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Links

• Sponsor maintained study web address

MeSH Terms

Interventions

tirabrutinib

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: July 1, 2021
• Study Start: December 29, 2021
• Primary Completion: January 27, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (39)