Clinical trial NCT03684980: LTA Pilot Study of Glucarpidase in Patients With Central Nervous System Lymphoma
Official title: LTA Pilot Study of Glucarpidase in Patients With Central Nervous System Lymphoma
Conditions: Central Nervous System Lymphoma
Summary: The purpose of this study is to test the effects of a drug called Voraxaze when it's routinely given in combination with methotrexate and rituximab, the standard treatment for CNSL.
Interventions:
description: (Cohort A) will receive MTX 3 g/m2 or (Cohort B) will receive MTX 8 g/m^2 (Cohort E) will receive MTX ≤ 3.5 g/ m2
name: Methotrexate
type: Drug
description: Patients will be treated with rituximab 500 mg/m^2.
name: Rituximab
type: Drug
description: Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.
name: leucovorin
type: Drug
description: Glucarpidase 2000 units. Arm E 1000 units.
name: Glucarpidase
other_name: Voraxaze
type: Drug
Study arms:
design_group_description: Patients will receive rituximab Day 1 (+/- 7 days) and MTX Day 2 (+/- 7 days) as per standard of care. Voraxaze will be administered each cycle 24 hours (+/- 2 h) after start of MTX infusion. Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8. Patients will be treated with rituximab 500 mg/m^2. (Cohort A) will receive MTX 3 g/m2. Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.
design_group_title: Arm A - Rituximab + MTX + Glucarpidase
design_group_type: Experimental
design_group_description: Patients will receive up to 8 cycles of treatment consisting of rituximab Day 1 (+/- 7 days) and MTX Day 2 (+/- 7 days) as per standard of care. Voraxaze will be administered each cycle 24 hours (+/- 2 h) after start of MTX infusion. Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8. Patients will be treated with rituximab 500 mg/m^2. (Cohort B) will receive MTX 8 g/m2. Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.
design_group_title: Arm B - Rituximab + MTX + Glucarpidase
design_group_type: Experimental
design_group_description: MTX ≤ 3.5 g/m2 will be administered on Day 1, along with pre- and post- hydration. Patients will return on Day 2 for continued hydration and glucarpidase 2000 units. Glucarpidase rapidly and sustainably reduces serum MTX levels >95% without crossing the blood brain barrier, effectively resulting in systemic MTX clearance. Patients will return for bloodwork on Day 3 to document MTX clearance. Arm Outpatient MTX Therapy in times of COVID-19 will only be a single-institution arm, only open at Memorial Sloan Kettering Cancer Center.
design_group_title: Arm C - HD-MTX (Arm Outpatient MTX Therapy in times of COVID-19)
design_group_type: Experimental
design_group_description: Up to 12 patients will be included in Arm D of this study. Cycles will be 14 days long. All patients will receive MTX 3.5 g/m2 administered Day 1 of each cycle (+/- 7 days, a minimum of 14 days required between doses). Glucarpidase will be administered 24 hours (+/- 2 hr) after start of MTX infusion except in cycles 1-2 of Cohort B. Dose of glucarpidase will be 2000 units in Cohort A (first 4 patients) and 1000 units in Cohort B (remaining 8 patients). Patients in Arm D will receive 8 cycles of treatment. Cycles 1 and 2 will be administered in patient while Cycles 3-8 may be in the outpatient setting. Concurrent chemotherapy such as vincristine, procarbazine, and/or ibrutinib may be administered at the investigator's discretion and in accordance with standard of care. In Cohort B, all cycles will be administered with rituximab 500 mg/m2. Rituximab should be administered prior to glucarpidase (window -4 days).
design_group_title: Arm D -Rituximab + MTX + Glucarpidase
design_group_type: Experimental
design_group_description: Study treatment consists of glucarpidase 1000u, to be administered at least 24 hours after start of standard of care MTX. Patients will have a standard of care methotrexate level drawn within 6 hours of planned glucarpidase administration to confirm eligibility (must reflect MTX > 100 nmol/L)
design_group_title: Arm E-glucarpidase 1000u + MTX
design_group_type: Experimental
Sponsor: Memorial Sloan Kettering Cancer Center
Collaborators: The University of Alabama at Birmingham
Drug name mappings:
name: 羧肽酶
lang: CN
name: Glucarpidase
lang: EN
name: グルカルピダーゼ（遺伝子組換え）
lang: JP
name: 亚叶酸钙
lang: CN
name: Leucovorin Calcium
lang: EN
name: ホリナートカルシウム
lang: JP
name: 利妥昔单抗
lang: CN
name: Rituximab
lang: EN
name: リツキシマブ（遺伝子組換え）
lang: JP
name: 甲氨蝶呤
lang: CN
name: Methotrexate
lang: EN
name: メトトレキサート
lang: JP