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High-dose methotrexate, leucovorin, and Voraxaze

High-dose methotrexate and leucovorin without Voraxaze (glucarpidase)

glucarpidase, high-dose methotrexate, leucovorin

standard of care, leucovorin every 6 hours

high-dose methotrexate, leucovorin

Andrew Saunders, MD

Suzanne Kincaid, CCRA

The purpose of this study is to investigate whether the administration of Voraxaze reduces exposure to leucovorin and its active metabolite to below the level achieved in patients who have not received Voraxaze.

Open-label Leucovorin Pharmacokinetic Study in Patients Receiving High Dose Methotrexate With or Without Voraxaze

An Open-Label Study to Assess the Pharmacokinetics of Leucovorin in Patients Receiving High Dose Methotrexate, With or Without Voraxaze Treatment

Geometric mean (6S)-leucovorin area under the plasma concentration vs. time curve from time 0 to the 3-hour time point.

BTG International Inc.

High-dose methotrexate, leucovorin, and glucarpidase

glucarpidase, high-dose methotrexate, leucovorin: single intravenous dose

A (High-dose Methotrexate, Leucovorin, and Glucarpidase)

High-dose methotrexate and leucovorin without glucarpidase

high-dose methotrexate, leucovorin: standard of care, leucovorin every 6 hours

B (High-dose Methotrexate and Leucovorin Without Glucarpidase)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Pre-glucarpidase (Arm A) or Pre-LV (Arm B) methotrexate plasma conc (umol/L)

SVP, Clinical Development

3 participants were excluded from the PK population (all from Arm A), hence why the total participants is 17, not 20.

Pharmacokinetics (PK) of Leucovorin

Drug: High-dose methotrexate (HDMTX) and leucovorin (LV) with a single bolus intravenous injection of 50 units/kg glucarpidase over 5 minutes.

HDMTX followed by intravenous LV administered at doses recommended in the clinical treatment protocols.

LV doses administered as recommended in the package insert for Leucovorin Calcium USP for patients with delayed early MTX elimination and/or evidence of acute renal injury, and should be based upon the pre-glucarpidase MTX concentration. LV doses are maintained for at least 48 hours after dosing with glucarpidase. After this it may be administered at doses recommended in the clinical treatment protocols and existing labeling for LV based on post-Voraxaze MTX concentrations. Patients required IV LV rescue therapy with either ≥15 mg or ≥10 mg/m2 every 6 hours.

Other Names:

Voraxaze, carboxypeptidase G2, high dose methotrexate, leucovorin

High-dose methotrexate (HDMTX) and leucovorin (LV) without glucarpidase

HDMTX followed by intravenous LV should be administered at doses recommended in the clinical treatment protocols and as per standard of care. LV should be given every 6 hours at a dose of ≤25 mg/m2.

Overall Study

50 Units/kg in a bolus intravenous injection over 5 minutes

Voraxaze (glucarpidase)

Paul Litka, MD

This protocol is for the treatment of toxic plasma methotrexate concentrations (\>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function

This treatment protocol will be available on a cost recovery basis to IRB-approved Investigators treating an eligible patient at any site in the US. In order to continue to make Voraxaze™ available following FDA approval and prior to being commercially available. Protherics needs to charge for the product, so there will be a cost to obtain Voraxaze™ under the Open-Label Treatment Protocol. Protherics is permitted under the FDA regulations (21 CFR 312.8) to charge for Voraxaze, to recover those costs associated with its manufacture, research and development, and handling, but do not include other commercial costs (profit).

Patient eligibility is based on MTX concentrations and laboratory values obtained per standard of care. Once an Investigator identifies a potential patient, he/she will contact the Voraxaze central call center (1-877-398-9829) to receive information regarding drug shipment. Eligible patients will have routine demographic, MTX, and Voraxaze therapy information collected.

Each patient will receive a single dose of Voraxaze 50 Units/kg in a bolus intravenous injection over 5 minutes. In addition to Voraxaze, patients will continue to receive standard of care treatment including leucovorin therapy, and supportive care such as hydration, alkalinization of urine and, if necessary, hemoperfusion/dialysis.

Treatment Protocol of Voraxaze for Patients Experiencing or at Risk of Methotrexate Toxicity

An Open-Label Treatment Protocol for the Use of Voraxaze as Adjunctive Treatment for Patients Experiencing or at Risk of Methotrexate Toxicity

CTI Clinical Trial and Consulting Services

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Open-label Leucovorin Pharmacokinetic Study in Patients Receiving High Dose Methotrexate With or Without Voraxaze	NCT00634504	Osteosarcoma Leukemia Lymphoma	glucarpidase, h... high-dose metho...	-	BTG International Inc.
Open-label Leucovorin Pharmacokinetic Study in Patients Receiving High Dose Methotrexate With or Without Voraxaze	NCT00634504	Osteosarcoma Leukemia Lymphoma	glucarpidase, h... high-dose metho...	-	BTG International Inc.
Treatment Protocol of Voraxaze for Patients Experiencing or at Risk of Methotrexate Toxicity	NCT00481559	Neoplasms	Voraxaze (gluca...	-	BTG International Inc.

Spots Global Cancer Trial Database for delayed elimination