Phase I Trial of Escalating High Dose Methotrexate Supported by Glucarpidase to Treat Patients With Primary Central Nervous Lymphoma (PCNSL)
- To determine the dose-limiting toxicity of methotrexate (MTX) when given in combination
with glucarpidase in patients with newly diagnosed primary CNS lymphoma (PCNSL).
- To determine the incidence of immediate reactions related to the use of glucarpidase in
- To define a safer, more practical, and simpler regimen for delivering multiple courses
of high-dose MTX using glucarpidase and 'short' leucovorin calcium rescue in these
- To monitor quality of life and mental function during and after therapy in these
- To use this regimen as a platform for phase III studies in PCNSL.
- To record disease response, duration of response, and overall survival of patients
treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of high-dose methotrexate (HD-MTX).
Patients receive HD-MTX IV over 4 hours on day 1. Beginning 22 hours after the start of
HD-MTX, patients receive glucarpidase IV over 15 minutes on day 2 followed by leucovorin
calcium orally or IV on days 2-7. Treatment repeats every 14 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.
Within 2-4 weeks after completion of study treatment, patients achieving maximum response
are stratified according to age (< 60 years vs ≥ 60 years) and may undergo whole brain
radiotherapy (WBRT) once daily, 5 days a week, for 3 to 5 weeks.
Patients undergo blood sample collection periodically to assess glucarpidase antibodies and
Patients are assessed for mucositis incidence and severity periodically, and complete
quality of life assessments using the EORTC QLQ-30 questionnaire and the Mini-Mental State
questionnaire at baseline, during, and after completion of study.
After completion of study treatment, patients are followed at 6 weeks after WBRT, every 3
months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually
Masking: Open Label, Primary Purpose: Treatment
Immediate toxicity (incidence of reactions to glucarpidase) as determined by the NCI CTC
Roderick Johnson, MD
Leeds General Infirmary