Combining Rituximab and Methotrexate with or without Lenalidomide for treating primary central nervous system lymphoma

Efficacy and Safety Study of Lenalidomide Plus Rituximab and Methotrexate Chemotherapy（R2-MTX） Versus Rituximab and Methotrexate Chemotherapy（R-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma: a Multicenter, Open-Label, Randomised Phase 2 Study

This study is testing if adding lenalidomide to the standard treatment of rituximab and methotrexate can help people with newly diagnosed primary central nervous system lymphoma live longer without their cancer getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: Rituximab, chemotherapy, Methotrexate
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT04481815 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label, randomized phase 2 study aims to evaluate the efficacy and safety of rituximab plus methotrexate with or without lenalidomide as first-line treatments for newly diagnosed primary central nervous system lymphoma (PCNSL). A total of 240 patients will receive either the combination of all three drugs or just rituximab and methotrexate over a series of cycles, followed by maintenance chemotherapy. The primary endpoint is the 2-year progression-free survival rate, with secondary endpoints including overall survival and 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 who have undergone prior treatment for PCNSL or those who are planned for autologous hematopoietic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could improve progression-free survival rates for patients with primary central nervous system lymphoma.

How similar studies have performed: Other studies have shown promising results with similar chemotherapy combinations in treating PCNSL, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma
2. Age range 18-75 years old.
3. Eastern Cooperative Oncology Group performance status 0 to 3.
4. Previously untreated. Patients treated with steroid alone are eligible.
5. Patient's who are not planned to undergo consolidation with autologous hematopoietic stem cell transplantation（HSCT）.
6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI.
7. Life expectancy of ≥ 3 months (in the opinion of the investigator).
8. Participants must be able to understand and be willing to sign a written informed consent document.
9. 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.
10. Women of childbearing potential must have a negative plasma pregnancy test upon study entry.
11. 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.
12. Adequate liver functions: Transaminase (AST/ALT) \< 3 X upper normal value \& Bilirubin \< 2 X upper normal value.
13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL.

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. Patients considered unsuitable to participate in the study by the researchers.

Where this trial is running

Hangzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Xianggui Yuan, MD,PhD

Conditions PCNSL; Lenalidomide