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Non-hodgkin LymphomaPhase 2NCT05998642

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

A Phase 2 study testing Methotrexate, Rituximab (where available) and Ibrutinib in people with Non-hodgkin Lymphoma, run by Canadian Cancer Trials Group at 8 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-hodgkin Lymphoma
What is being tested?
Methotrexate, Rituximab (where available) and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
8 sitesCanada
Study dates
13 Feb 2024to 31 Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • They have receivedMethotrexate +/- 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.
  • They have receivedUse of corticosteroids (topical are permitted) on study (except for short-term treatment of infusion reactions and nausea prophylaxis) is not permitted. Patients receiving corticosteroids may be eligible, providing:
  • They have receivedThey are receiving not more than dexamethasone 8mg/day (or equivalent)
  • They have received 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).
  • Patients must have adequate organ and marrow function measured within 7 days prior to enrollment including: Absolute neutrophils ≥ 1.0 x 10^9/L (independent of growth factor support); Platelets ≥ 75 x 10^9/L; Bilirubin ≤ 1.5 x UNL; ALT ≤ 3.0 x UNL (if AST >3 x UNL consult with CTG re: eligibility); Creatinine clearance ≥ 50 mL/min
  • Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaire in either English or French
  • Patients must be accessible for treatment and follow up. Patients enrolled on this trial must be treated and followed at the participating centre
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method.

Who cannot join

  • 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 receivedThey 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
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  • They have receivedHIV 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
  • Supplements containing fish oil or vitamin E, and grapefruit juice should be avoided
  • Live attenuated vaccination administered within 30 days prior to enrollment, or within 30 days prior to start date of pre-study methotrexate +/- rituximab for participants who receive one cycle before enrollment
  • Patients with clinically significant cardiac disease, including:
  • angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months;
  • history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy;
  • uncontrolled hypertension (per Canadian guidelines);
  • atrial or ventricular arrhythmias; patients with controlled atrial fibrillation are eligible
  • Patients with distant clinically significant cardiac history should have a LVEF ≥ 50% Baseline LVEF is not required for patients with only a cardiac history of hypertension which is now controlled.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Annette Hay contact

613-533-6430

ahay@ctg.queensu.ca

8 sites in 1 country

Canada8 sites, 8 recruiting

  • Arthur J.E. Child Comprehensive Cancer Centre

    Calgary, Alberta, T2N 5G2

    Robert Puckrin, 403 944-5222

    Recruiting

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

    Graeme Fraser, 905 575-7820

    Recruiting

  • The Research Institute of the McGill University

    Montreal, Quebec, H4A 3J1

    Kelly Davison, 514 934-1934 ext. 31558

    Recruiting

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

    David A. MacDonald

    Recruiting

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

    Québec, Quebec, G1J 1Z4

    Jean-Francois Larouche

    Recruiting

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

    Magdi Ali, 306 766-2691

    Recruiting

  • University Health Network

    Toronto, Ontario, M5G 2M9

    Anca Prica, 416 946-4501 ext. 2249

    Recruiting

  • BCCA - Vancouver

    Vancouver, British Columbia, V5Z 4E6

    Diego Villa Restrepo, 604 877-6000 ext. 2740

    Recruiting

Other trials in Canada

About this study

Official title: A Phase 2 Study of Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary Central Nervous System Lymphoma

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).

Read the detailed description

If a patient decides to take part in this study, the patient will get 3 months of treatment with methotrexate and ibrutinib as well as rituximab (if rituximab is given for PCNSL in the applicable province). This will be followed by treatment with ibrutinib alone for up to 2 years of total treatment time.

After finishing study treatment, and even if patients stop treatment early, the study doctor will continue to follow the patient's condition for the rest of their life or until all study results are known (in approximately 6 years), watch for side effects and keep track of the patient's health. If there are any side effects that may be related to ibrutinib, the patient will be asked to come back to the clinic every 3 months until side effects improve. If there are no side effects from ibrutinib the patient will be asked to come back to clinic every 6 months until cancer worsens, and then every 6 months may be contacted by phone.

Being tested
Methotrexate, Rituximab (where available), Ibrutinib
Keywords
Central Nervous System
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    3.5mg/m2 IV

  • Rituximab (where available)Drug

    375mg/m2 / 1400mg IV or SC

  • IbrutinibDrug

    Dose and schedule assigned at enrollment (oral)

Study groups in NCT05998642
Study groupRoleWhat they receive
Methotrexate, Ibrutinib +/- RituximabExperimentalCycles 1-6, q14 days Day 1: Methotrexate + Rituximab Days 6-14: Ibrutinib daily orally. Monotherapy Maintenance Cycles 7+, q28 days Day 1-28; Ibrutinib daily orally.
Receives: Drug: Methotrexate; Drug: Rituximab (where available); Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. One year progression-free survival (PFS)

    Measured: 5 years

Secondary outcomes (7)

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

    Measured: 5 years

  2. 1-year event-free survival (EFS)

    Measured: 5 years

  3. 2-year progression-free survival

    Measured: 5 years

  4. Overall survival (OS)

    Measured: 5 years

  5. Number and severity of adverse events

    Measured: 5 years

  6. To determine the impact on cognitive functioning of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-Cog

    Measured: 5 years

  7. To determine the impact on health-related quality of life of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL using FACT-BR

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2023
  2. Study start13 Feb 2024
  3. Primary completion31 May 2028 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05998642
Sponsor's protocol ID
I244
Status last verified
Nov 2026
First submitted
11 Aug 2023
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate, Rituximab (where available) and Ibrutinib in people with Non-hodgkin Lymphoma, run by Canadian Cancer Trials Group at 8 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Annette Hay (613-533-6430, ahay@ctg.queensu.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

One year progression-free survival (PFS) (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05998642.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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