NCT04841434

A Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with CNSL

An Open Label, Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with Central Nervous System Lymphoma and with Impaired Renal Function Being Treated with High-dose Methotrexate

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Charite University, Berlin, Germany · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I-II trial is intented to demonstrate tolerability (i.e. absence of severe non-hematological toxicity) and efficacy of intended intervention with repeated doses of Voraxaze, in addition to leucovorin (LV), in patients with renal impairment or renal failure during previous HD-MTX therapy. Patients will receive up to 6 cycles of HD-MTX treatment with 14 days between cycles (a maximum delay of 28 days is permitted in order to allow time for a patient to recover from the previous cycle).

Detailed description

MTX is used either alone or as part of a combined chemotherapy protocol either in standard or high doses in the treatment of a range of cancers and other diseases. Dose escalation will be performed using three dose levels of MTX: Level 1: 3.0 g/m2 Level 2: 3.5 g/m2 Level 3: 4.0 g/m2 Up to 6 patients will be treated at each dose level; each will receive a maximum of 6 cycles of treatment. The dose may be increased in Cycle 3 in individual patients to the next level, if renal function is adequate (GFR ≥ 40 mL/min, or in the case of decreased GFR, the decrease is \<10% compared with the pre-treatment value), and absence of grade 3 or 4 non-hematological toxicities.

Conditions

• CNS Lymphoma

Interventions

Type	Name	Description
DRUG	Voraxaze Injectable Product	High-dose Methotrexat Infusion: MTX is given at a dose according to the allocated dose level cohort as a 4-hour IV infusion. HD-MTX cycles (up to 6) should be repeated every 14 days, provided that the patient has recovered (i.e., hematopoietic reconstitution) between cycles. A delay of up to 28 days between cycles is permitted in order to allow patients to recover from the preceding dose of MTX. In patients with a decline of the GFR to \<40 mL/min, or in the case of decreased GFR, the decrease is \>50% compared with the pretreatment value, treatment will be terminated. At the start of Cycle 3 the dose of MTX can be escalated to the next level if MTX has been well-tolerated according to the criteria described under dose escalation. Voraxaze: 2000 Units in patients weighing ≤100kg and at least 20 Units per kg body weight in patients weighing \>100kg is given in each HD-MTX cycle as a slow IV injection at 24 hours (+/- 2 hours) after the start of HD-MTX infusion.

Timeline

• Start date: 2021-06-01
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2021-04-12
• Last updated: 2025-01-06

Locations

1 site across 1 country: Germany