Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma

NCT05998642 | Recruiting Phase 2 DMC

• 1 other identifier: I244
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

Brief Summary

This study is being done to answer the following question: Can the addition of a new drug to the usual treatment lower the chance of primary central nervous system lymphoma growing or spreading? This study is being done to find out if this approach is better or worse than the usual approach for this type of cancer. The usual approach is defined as the care most people get for Primary Central Nervous System Lymphoma (PCNSL).

Conditions

Non-hodgkin Lymphoma

Keywords

Central Nervous System

Outcome Measures

Primary Outcomes (1)

• One year progression-free survival (PFS)

  5 years

Secondary Outcomes (7)

• Overall Response Rate (ORR = CR+CRu+PR) and complete response (CR) rate

  5 years

• 1-year event-free survival (EFS)

  5 years

• 2-year progression-free survival

  5 years

• Overall survival (OS)

  5 years

• Number and severity of adverse events

  5 years

Study Arms (1)

Methotrexate, Ibrutinib +/- Rituximab

EXPERIMENTAL

Cycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally

Drug: Methotrexate; Drug: Rituximab (where available); Drug: Ibrutinib

Interventions

Methotrexate DRUG

3.5mg/m2 IV

Methotrexate, Ibrutinib +/- Rituximab

Rituximab (where available) DRUG

375mg/m2 / 1400mg IV or SC

Methotrexate, Ibrutinib +/- Rituximab

Ibrutinib DRUG

Dose and schedule assigned at enrollment

Methotrexate, Ibrutinib +/- Rituximab

Eligibility Criteria

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

You may qualify if:

• Patients must have histological or cytological evidence of primary central nervous system (CNS) lymphoma (PCNSL); patients with vitreo-retinal lymphoma (NHL) or cerebrospinal fluid (CSF) positive disease are eligible providing there is CNS involvement on MRI compatible with PCNSL
• Patients must be 18 years of age or older
• Patients must be ineligible (≥65 years old or comorbidities) for high-dose chemotherapy and autologous stem cell transplantation. Patients must be considered fit, as determined by the treating physician, to receive high dose methotrexate, ibrutinib and rituximab as per protocol
• Patients must have consented to the release of a tumour block from their brain tumour, if available (see Section 12.0). The centre/pathologist must have agreed to the submission of the specimen(s).
• Presence of radiological documented disease. Patients believed to have residual disease following a complete resection, even if radiology is negative or equivocal, are eligible provided they are planned for standard of care methotrexate/rituximab.
• No prior systemic therapy other than the following situations:
• Methotrexate +/- rituximab: Patients may have received one cycle of methotrexate with or without rituximab as standard of care therapy, but must be enrolled no longer than 4 weeks after first dose of methotrexate corticosteroids for PCNSL is permitted.
• Use of corticosteroids (topical are permitted) on study (except for short-term treatment of infusion reactions and nausea prophylaxis) is not permitted. Patients receiving corticosteroids me be eligible, providing:
• they are receiving not more than dexamethasone 8mg/day (or equivalent)
• The corticosteroid will be tapered and completely discontinued within 7 days of starting the study protocol treatment. Patients who would require continued or concurrent treatment with systemic steroids are not eligible.
• Intrathecal therapy: Patients may have received intrathecal therapy at the time of diagnostic lumbar puncture. No washout period is needed prior to enrollment.
• Previous major surgery is permitted provided that surgery occurred at least 28 days prior to patient enrollment and that wound healing has occurred. The 28 day cut-off does not apply to surgery for PCNSL; treatment may begin following brain biopsy/resection when deemed safe by the treating investigator
• No prior radiation therapy for PCNSL is allowed
• ECOG performance status 0-2, and ECOG 3 permitted if secondary to primary CNS lymphoma and expected to reverse with treatment
• Patients must be able to swallow oral medications and have no known gastrointestinal disorders that may interfere with absorption (such as malabsorption).

You may not qualify if:

• Patients with secondary central nervous system non-Hodgkin lymphoma (NHL).
• Patients with significant third space accumulation (pleural effusions, ascites) which cannot be adequately drained in advance of methotrexate administration
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. However, patients on active anticancer therapy for other advanced or metastatic malignancies are not eligible.
• Patients with a known hypersensitivity to the study drugs or their components
• Active, uncontrolled bacterial, fungal, or viral infection within 7 days prior to enrollment. Patients with hepatitis B serology suggestive of past infection (for example anti-HB-c positive but HBsAG and anti-HBs negative) are eligible if they are HBV DNA negative are being or will be concurrently treated with anti-viral therapy. Patients with a history of hepatitis C which has been treated and is no longer active are eligible. Patients with known human immunodeficiency virus (HIV) with CD4 count \< 350 cells/microliter are ineligible. Patients who are HIV positive are eligible, provided:
• They have received antiretroviral therapy for at least 4 weeks prior to enrollment, and the anti-viral drugs used are not known to have clinically relevant drug-drug interactions with ibrutinib AND
• HIV viral load must be \< 400 copies/ml within 16 weeks prior to enrollment AND No history of opportunistic infections within the past year
• Serious illnesses or medical conditions which would not permit the patient to be managed according to protocol
• Patients may not receive concurrent treatment with other anti-cancer therapy or investigational agents while on protocol therapy
• Patients with prior allogenic bone marrow transplant or double umbilical cord blood transplantation.
• Pregnant or breastfeeding women
• Patients requiring:
• Anticoagulation with warfarin or equivalent vitamin K antagonists
• Continued requirement for therapy with a strong CYP3A inhibitor or inducer (see trial webpage for list)
• Corticosteroid treatment with \> 8mg of dexamethasone (or equivalent) at the time of enrollment

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Janssen Inc.: collaborator

Study Sites (8)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

The Research Institute of the McGill University

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Methotrexate; Rituximab; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jean-Francois Larouche

  CHU de Quebec-Hopital l'Enfant-Jesus (HEJ), Quebec City, QC Canada

  STUDY CHAIR

• Anca Prica

  University Health Network-Princess Margaret Hospital, Toronto, ON Canada

  STUDY CHAIR

Central Study Contacts

Annette Hay

CONTACT

613-533-6430; ahay@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2023
• First Posted: August 21, 2023
• Study Start: February 13, 2024
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 14, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8)