Combination treatment for newly diagnosed primary central nervous system lymphoma

Orelabrutinib, Rituximab and Methotrexate (OR-MTX) in Newly Diagnosed Primary Central Nervous System Lymphoma: a Single Arm, Multicenter, Phase 2 Study

This study is testing a new combination of treatments for people with newly diagnosed primary central nervous system lymphoma to see if it helps them respond better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: Rituximab, Orelabrutinib, chemotherapy, Methotrexate
• Locations: 1 site (Hanzhou, Zhejiang)
• Trial ID: NCT05600660 on ClinicalTrials.gov

What this trial studies

This phase 2 study evaluates the efficacy and safety of a combination of Orelabrutinib, Rituximab, and Methotrexate as first-line treatment for patients with newly diagnosed primary central nervous system lymphoma. The study will enroll 28 participants who will receive 6 cycles of induction chemotherapy, followed by maintenance therapy with Orelabrutinib for up to one year. Eligible patients may also undergo autologous Hematopoietic Stem Cell Transplantation if they meet the criteria. The primary goal is to assess the objective response rate, while secondary outcomes include progression-free survival, overall survival, and monitoring of adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed primary central nervous system lymphoma who have not received prior treatment.

Not a fit: Patients with a performance status above 3 or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve outcomes for patients with primary central nervous system lymphoma.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating lymphoma, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma Age range 18-75 years old.
2. Eastern Cooperative Oncology Group performance status 0 to 3.
3. Previously untreated. Patients treated with steroid alone are eligible.
4. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.
5. Life expectancy of ≥ 3 months (in the opinion of the investigator).
6. Participants must be able to understand and be willing to sign a written informed consent document.
7. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose.

   Women of childbearing potential must have a negative plasma pregnancy test upon study entry.
8. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of normal.
9. Adequate liver functions: Transaminase (AST/ALT) \< 3 X upper normal value \& Bilirubin \< 2 X upper normal value.
10. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL.
11. Must be able to tolerate lumbar puncture and MRI/CT.
12. Ability to swallow oral medications.

Exclusion Criteria:

1. Patient with systemic, non-CNS lymphoma metastatic to the CNS.
2. Patient is concurrently using other approved or investigational antineoplastic agents.
3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104), hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases include but not limited to HIV.
4. Patient is allergic to components of the study drug.
5. Patient has an active concurrent malignancy requiring active therapy.
6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening.
7. Patient is known to have an uncontrolled active systemic infection.
8. Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin(hCG) laboratory test of \> 5 mIU/mL.
10. The patient is unwell or unable to participate in all required study evaluations and procedures.
11. Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results.
12. History of intracranial hemorrhage or clinically significant stroke within 6 months prior to first day of study treatment
13. History of significant gastrointestinal disease that would limit absorption of oral medications.
14. Warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists. Patients must be off warfarin-derivative anticoagulants for at least seven days prior to starting the study drug. Use of low molecular weight heparin and novel oral anticoagulants (eg. rivaroxaban, apixaban) is permitted if required.
15. Concurrent use of a moderate or strong inhibitor or inducer of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers prior to starting the study drug.
16. Known bleeding diathesis (e.g. von Willebrand's disease), hemophilia, or active bleeding.
17. History of invasive fungal infection, including invasive aspergillosis, or known active tuberculosis.
18. Patients considered unsuitable to participate in the study by the researchers.

Where this trial is running

Hanzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University — Hanzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Wenbin Qian, prof.

Conditions: Primary Central Nervous System Lymphoma, Orelabrutinib, Methotrexate, Lenalidomide