LTA Pilot Study of Glucarpidase in Patients With Central Nervous System Lymphoma

Conditions

• Central Nervous System Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Methotrexate — DRUG
  (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
• Rituximab — DRUG
  Patients will be treated with rituximab 500 mg/m\^2.
• leucovorin — DRUG
  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.
• Glucarpidase — DRUG
  Glucarpidase 2000 units. Arm E 1000 units.

Study Details

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.

Key Dates

Start date

Nov 14, 2018

Status verified

Apr 2026

Primary completion

Nov 30, 2027

Completion

Nov 30, 2027

Study Design

Enrollment

58 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A - Rituximab + MTX + Glucarpidase
  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.
• Experimental: Arm B - Rituximab + MTX + Glucarpidase
  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.
• Experimental: Arm C - HD-MTX (Arm Outpatient MTX Therapy in times of COVID-19)
  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.
• Experimental: Arm D -Rituximab + MTX + Glucarpidase
  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).
• Experimental: Arm E-glucarpidase 1000u + MTX
  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)

Primary Outcome Measure

number of patients that have significant reduction of serum methotrexate levels [ Time Frame: 1 year ]

Locations (11)

Find similar trials in Birmingham, AL

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