Evaluation of Lisocabtagene Maraleucel as First-Line Therapy in Transplant-Ineligible Patients with Primary Central Nervous System Lymphoma

The primary objective of this study is to evaluate the efficacy of lisocabtagene maraleucel in preventing disease progression within one year of administration in patients with newly diagnosed primary central nervous system lymphoma who are ineligible for autologous stem cell transplant. 5 The secondary objectives include:

• Assessment of additional therapeutic efficacy.
• Evaluation of safety.
• Analysis of the impact on quality of life.

This study involves 24 participants diagnosed with Primary Central Nervous System Lymphoma. The study population includes both male and female individuals. Inclusion requires a confirmed diagnosis via laboratory tests and an ECOG performance score between 0 and 2. Eligible participants must be unable to undergo autologous stem cell transplant and must be suitable for a treatment regimen involving high-dose methotrexate. Additionally, subjects must have received only standard treatments previously and must exhibit either a complete or partial clinical response prior to enrollment.

This Phase II clinical trial evaluates the efficacy and safety of lisocabtagene maraleucel as a first-line therapy for adults with newly diagnosed primary central nervous system lymphoma who are ineligible for autologous stem cell transplant. The study aims to determine the proportion of participants without disease progression or death within 12 months following the administration of the investigational product. Eligible participants must be 18 years or older, have a confirmed diagnosis via laboratory tests, and possess an ECOG performance score between 0 and 2. Participants must also be suitable for a treatment regimen including high-dose methotrexate and have achieved complete or near-complete remission following standard treatments prior to enrollment. The research methodology includes the assessment of secondary endpoints such as progression-free survival, time to new cancer treatment, overall survival, complete response, and the duration of response, alongside evaluations of quality of life and the frequency of adverse events. The trial is estimated to occur between November 2025 and October 2028.

The investigational product is lisocabtagene maraleucel, administered as a cell suspension for injection via the intravenous route at a dose of 100 units.

Background therapies used in the study include rituximab administered by injection at a dose of 9999 mg/m2. Methotrexate is provided via injection at a dosage of 9999 mg/ml. Temozolomide is administered orally at a dose of 9999 mg. Calcium folinate is utilized as both an oral agent at 9999 mg and as a solution for injection at 9999 mg/ml. Cyclophosphamide is administered through intravenous infusion at a dose of 300 mg/m2. Tocilizumab is delivered via the intravenous route at a dose of 9999 mg/ml. Procarbazine is administered orally at a dose of 9999 mg. Fludarabine is provided via intravenous administration at a dose of 30 mg/m2.

The primary efficacy endpoint is the proportion of participants experiencing disease progression or death within 12 months following the administration of lisocabtagene maraleucel in patients with newly diagnosed primary central nervous system lymphoma.

Secondary endpoints include:

• Time to disease progression.
• Time to initiation of subsequent anti-lymphoma therapy.
• Time to death from any cause following enrollment.
• The proportion of participants achieving complete response or partial response at any time post-treatment prior to disease progression, initiation of new treatment, or study termination.
• The proportion of participants with no detectable signs of cancer.
• Duration of response.
• Impact of treatment on quality of life.
• Assessment of adverse events, including frequency and severity.