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Cancer | Individualized High Dose Methotrexate to Treat Cancer in Children Who Have a Significant Risk for Side Effects to Methotrexate

Cancer research study

What is the primary objective of this study?

Pediatric cancer patients are being asked to take part in this study who have a cancer that is treated with high doses of the drug methotrexate (MTX). In addition, these patients have either had significant side effects to methotrexate in the past or their doctor thinks that they are at high risk for side effects from receiving methotrexate. Methotrexate is a cancer-fighting drug that is very important in the treatment of leukemia. In this study, investigators are testing a new method of giving high dose methotrexate to cancer patients which may reduce the chances that the level of methotrexate in the blood is too high. When the levels are too high this is thought to lead to an increase in side effects. Side effects are unintended and unwanted results of treatment. The initial ordered amount of methotrexate and the period over which methotrexate is given will not change from the current standard of care (meaning what is usually done by doctors, and would likely be done if the patient was not on this study). This study is testing a new method of monitoring and potentially adjusting the final amount of methotrexate that the patient will end up receiving based on levels of methotrexate in the blood in the first 24 hours in order to try to prevent side effects in patients with a previous history of side effects from methotrexate or who are at high risk for having side effects. On this study the investigators will check methotrexate levels in the blood 2 hours after the patient starts receiving the drug and the investigators will lower the dose of methotrexate if needed. Investigators will do the same thing again 6-8 hours later. Investigators will also collect an optional blood sample from the patient because the investigators want to study how genetic (DNA) differences are involved in how the body processes methotrexate.

Who is eligible to participate?

Inclusion Criteria: 1. Age: Patients must be greater than or equal to 365 days and less than 23 years of age at the time of enrollment. 2. Diagnosis: Patients with any malignancy who will receive high dose methotrexate (HDMTX) given as a 5 g/m2 infusion over 24 hours and a history of ≥ 1 of the following: - Documented decreased renal function, defined as Creatinine greater than 1.5 x baseline or glomerular filtration rate (GFR) <65ml/min/1.73m2. - History of prior nephrotoxicity with HDMTX as evidence by increased creatinine to 1.5 x baseline or need for dialysis or carboxypeptidase - History of Grade 3 adverse event (AE) related to HDMTX (mucositis, myelosuppression, nephrotoxicity, hepatotoxicity) based on the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 - Provider concern patient is at risk for MTX toxicity, such as a prior history of treatment with nephrotoxic chemotherapy, history of HDMTX-related neurotoxicity, or antimicrobial/antifungal therapy Exclusion Criteria: 1. Unable to draw labs for HDMTX serum concentration 2. Enrollment on a protocol (COG or other) which restricts proposed dose modifications 3. Patients with Trisomy 21 4. Patients with greater than grade 1 neurologic toxicity at the time of enrollment that is attributed to unresolved prior methotrexate toxicity 5. Patients with greater than or equal to grade 3 chronic kidney disease at enrollment (eGFR or creatine clearance (CrCl) less than 30ml/min/1.73m2)

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Cancer

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:MethotrexatePatients will receive 5g/m^2 high dose methotrexate as a 24 hour infusion. The methotrexate level in the blood will be checked at two times during the 24-infusion. The dose will be reduced based on the level in the blood.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Individualized High Dose MethotrexateIndividualized high dose methotrexate given as a 24-hour infusion.

Study Status

Recruiting

Start Date: December 2013

Completed Date: June 2018

Phase: N/A

Type: Interventional

Design:

Primary Outcome: Incidence of success (achieving an end infusion peripheral blood methotrexate concentration between 50-80 μM)

Secondary Outcome: Incidence of nephrotoxicity

Study sponsors, principal investigator, and references

Principal Investigator: Jennifer H Foster, MD

Lead Sponsor: Baylor College of Medicine

Collaborator: Texas Children's Cancer Center

More information:https://clinicaltrials.gov/show/NCT02076997

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