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

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

NCT ID: NCT05998642

Condition: Non-hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Rituximab
Methotrexate
Ibrutinib

Conditions: Keywords:
Central Nervous System

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Methotrexate
Description: 3.5mg/m2 IV
Arm group label: Methotrexate, Ibrutinib +/- Rituximab

Intervention type: Drug
Intervention name: Rituximab (where available)
Description: 375mg/m2 / 1400mg IV or SC
Arm group label: Methotrexate, Ibrutinib +/- Rituximab

Intervention type: Drug
Intervention name: Ibrutinib
Description: Dose and schedule assigned at enrollment
Arm group label: Methotrexate, Ibrutinib +/- Rituximab

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).

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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). - No prior systemic therapy other than corticosteroids for PCNSL is permitted. Use of corticosteroids to control symptoms of PCNSL is allowed, but the patient must be on a maximum dose of dexamethasone 8mg/day (or equivalent) or less at the time of enrolment. Patients must wean off the steroids within 7 days of starting the study protocol treatment - 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 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. Exclusion Criteria: - 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 are eligible if they are HBV DNA negative and 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: 1. Anticoagulation with warfarin or equivalent vitamin K antagonists 2. Continued requirement for therapy with a strong CYP3A inhibitor or inducer (see trial webpage for list) 3. Corticosteroid treatment with > 8mg of dexamethasone (or equivalent) at the time of enrollment 4. Supplements containing fish oil or vitamin E, and grapefruit juice should be avoided - Live attenuated vaccination administered within 30 days prior to 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%

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: BCCA - Vancouver

Address:
City: Vancouver
Zip: V5Z 4E6
Country: Canada

Status: Recruiting

Contact:
Last name: Diego Villa Restrepo

Phone: 604 877-6000

Phone ext: 2740

Facility:
Name: Ottawa Hospital Research Institute

Address:
City: Ottawa
Zip: K1H 8L6
Country: Canada

Status: Recruiting

Contact:
Last name: David A. MacDonald

Facility:
Name: University Health Network

Address:
City: Toronto
Zip: M5G 2M9
Country: Canada

Status: Recruiting

Contact:
Last name: Anca Prica

Phone: 416 946-4501

Phone ext: 2249

Facility:
Name: The Research Institute of the McGill University

Address:
City: Montreal
Zip: H4A 3J1
Country: Canada

Status: Not yet recruiting

Contact:
Last name: Kelly Davison

Phone: 514 934-1934

Phone ext: 31558

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

Address:
City: Quebec City
Zip: G1J 1Z4
Country: Canada

Status: Recruiting

Contact:
Last name: Jean-Francois Larouche

Start date: February 13, 2024

Completion date: December 31, 2028

Lead sponsor:
Agency: Canadian Cancer Trials Group
Agency class: Other

Collaborator:
Agency: Janssen Inc.
Agency class: Industry

Source: Canadian Cancer Trials Group

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05998642