NCT04514393

Ibrutinib With Methotrexate and Temozolomide for Patients With Newly Diagnosed Primary CNS Lymphoma

Phase II Study of Combination Treatment of Methotrexate, Ibrutinib, and Temozolomide (MIT Regimen) in Patients With Newly Diagnosed Primary CNS Lymphoma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: Huiqiang Huang · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the study is to test the efficacy and tolerability of a combination treatment of methotrexate, ibrutinib, and temozolomide (MIT regimen) in treating patients who have newly-diagnosed primary CNS lymphoma.

Detailed description

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal Non-Hodgkin Lymphoma. Induction treatment of PCNSL in most reported single-arm or randomized trials includes high-dose methotrexate (HD-MTX)-based therapy, temozolomide, with or without cytarabine and the anti-CD20 antibody rituximab. A better combination remains undefined. Treatment is associated with considerable morbidity and disease recurrences with a 5-year survival of approximately 40%. The BTK inhibitor ibrutinib has shown antitumor activity in patients with recurrent or refractory PCNSL. However, tumor responses to single-agent ibrutinib in CNS lymphoma are often incomplete or transient. Efficacy and safety of ibrutinib in combination with cytotoxic agents are worth to be discovered. Grommes et al.have shown ibrutinib in combination with methotrexate and rituximab are safe and shows promising activity in recurrent/refractory CNS lymphoma. In comparison to their prior study with single-agent ibrutinib, the radiographic response of r/r PCNSL was higher with the ibrutinib/HD-MTX/rituximab combination regimen and PFS was longer with the combination therapy. The study has shown that ibrutinib combined with chemotherapy were superior to ibrutinib single agent and overcome the transient effect of ibrutinib in relapsed PCNSL. However, there are some limitations in interpreting Grommes' study results, especially the heterogeneous patient population with inclusion of both PCNSL and SCNSL. Most recently, the role of rituximab in PCNSL has become clearly. In the HOVON 105/ALLG NHL 24 study, the addition of rituximab to a methotrexate-based regimen did not demonstrate a significant benefit on clinical outcome. We therefore initiate this study aim to evaluate the activity and safety of ibrutinib in combination with Methotrexate and temozolomide (MIT regimen) in newly diagnosed PCNSL patients.

Conditions

• Primary Central Nervous System Lymphoma
• PCNSL
• Non Hodgkin Lymphoma

Interventions

Type	Name	Description
DRUG	Methotrexate	Intravenous methotrexate at 3.5g/m2 (standard hydration/leucovorin support) will be given on day 1 of all cycles，for up to 4 cycles.
DRUG	Ibrutinib	Oral ibrutinib will be given at a dose of 560 mg daily and will be continued daily after completion of methotrexate and temozolomide.Ibrutinib is continued until disease progression, intolerable toxicity or death.
DRUG	Temozolomide	Oral temozolomide will be given at 150mg/m2 from day1 to day 5 every 4 of all cycles，for up to 4 cycles.

Timeline

• Start date: 2020-10-10
• Primary completion: 2022-09-01
• Completion: 2024-06-01
• First posted: 2020-08-14
• Last updated: 2022-04-07

Locations

3 sites across 1 country: China