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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

Acute Kidney Injury

Acute Graft Versus Host Disease

Anti-Infective Agents

Amino Acids

Cystatins

Protease Inhibitors

HIV Protease Inhibitors

Cysteine

blood methotrexate level and Cystatin C level

Hosam H Khalaf, Doctor

Mai M Abd Elkader, lecturer

Maha A Helal, Professor

This study aims to:

1. Evaluation of high dose methotrexate related toxicities among children admitted to Sohag Oncology Centre.
2. Role of methotrexate blood level in prediction of high dose methotrexate related toxicities.
3. Role of Cystatin C as a predictor for acute kidney injury in high dose methotrexate related toxicities.
4. Factors affecting outcome of high dose methotrexate related toxicities.

It is a prospective observational study will be carried out on children receiving high dose methotrexate in Sohag Oncology Centre with one-year observation starting from January 2024.

All children receiving high dose methotrexate in Sohag Oncology Centre and fulfill the study inclusion criteria with one-year observation starting from January 2024. Informed consent will be taken from the parents/guardians.

A Prepared sheet to collect data related to this study that include:

1. Socio-demographic data: e.g. age, sex, residence in addition to dose of MTX and tumor type.
2. General and systemic manifestations: gastrointestinal manifestations, neurological manifestations, respiratory and hematological manifestations.
3. Investigations: blood samples will be collected for CBC, Urea, Creatinine, ALT, AST, Methotrexate level and Cystatin C.
4. Treatment lines: fluid, folinic acid, alkalinization of urine, blood elements, hemodialysis and colony stimulating factors.
5. Outcome: complete recovery, residual effects, complications or death.

Evaluation of High Dose Methotrexate Toxicity

Evaluation of High Dose Methotrexate Toxicity in Correlation With Blood Methotrexate Level and the Role of Cystatin C in Prediction of Acute Kidney Injury in Pediatric Malignancies

Venous blood will be collected under complete aseptic condition about 5 milliliters to measure serum methotrexate level using drug analyzer then the level of methotrexate will be used as apredictor to identify high dose methotrexate related toxicities in pediatric malignancies We will see if the test could predict the occurrence of toxicities before it happens or not

Venous samples will be collected about 3 milliliters under complete aseptic condition then centrifuged then the level of Cystatin C will be measured and will be used as abiomarker to detect acute kidney injury associated with high dose methotrexate related toxicities We will see if the test could predict occurrence of acute kidney injury before it happens or not

Sohag University

assistant lecturer

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.
Evaluation of High Dose Methotrexate Toxicity	NCT06123403	Methotrexate To...	blood methotrex...	1 Year - 18 Years	Sohag University
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.
Evaluation of High Dose Methotrexate Toxicity	NCT06123403	Methotrexate To...	blood methotrex...	1 Year - 18 Years	Sohag University

Spots Global Cancer Trial Database for methotrexate toxicity