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

NCT02076997 | Completed Results DMC

• 1 other identifier: H-33119
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer

Keywords

Cancer; High Dose Methotrexate

Outcome Measures

Primary Outcomes (1)

• Incidence of Success (Achieving an End Infusion Peripheral Blood Methotrexate Concentration Between 50-80 μM)

  1a) Calculate the incidence of success with the new protocol (achieving an end infusion peripheral blood methotrexate concentration between 50-80 μM)

  1 month

Secondary Outcomes (5)

• Incidence of >Grade 3 Nephrotoxicity

  2.5 months

• Incidence of Neurotoxicity

  2.5 months

• Incidence of Mucositis

  2.5 months

• Incidence of Hepatoxicity

  2.5 months

• Incidence of Myelosuppression

  2.5 months

Other Outcomes (2)

• Description of the Genotype of Various Methotrexate Metabolizing SNPs

  4 weeks

• Examination of Predictors of Success in Achieving Goal Concentration of Methotrexate

  4 weeks

Study Arms (1)

Individualized High Dose Methotrexate

EXPERIMENTAL

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

Drug: Methotrexate

Interventions

Methotrexate DRUG

Patients 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.

Individualized High Dose Methotrexate

Eligibility Criteria

• Age: 1 Year - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be greater than or equal to 365 days and less than 23 years of age at the time of enrollment.
• 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

You may not qualify if:

• Unable to draw labs for HDMTX serum concentration
• Enrollment on a protocol (COG or other) which restricts proposed dose modifications
• Patients with Trisomy 21
• Patients with greater than grade 1 neurologic toxicity at the time of enrollment that is attributed to unresolved prior methotrexate toxicity
• 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)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Texas Children's Cancer Center: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Foster JH, Thompson PA, Bernhardt MB, Margolin JF, Hilsenbeck SG, Jo E, Marquez-Do DA, Scheurer ME, Schafer ES. A prospective study of a simple algorithm to individually dose high-dose methotrexate for children with leukemia at risk for methotrexate toxicities. Cancer Chemother Pharmacol. 2019 Feb;83(2):349-360. doi: 10.1007/s00280-018-3733-2. Epub 2018 Nov 28.

  PMID: 30488179 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Methotrexate

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jennifer Foster
• Organization: Baylor College of Medicine

jhfoster@texaschildrens.org

832-824-4646

Study Officials

• Jennifer H Foster, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 4, 2014
• Study Start: January 1, 2014
• Primary Completion: May 30, 2017
• Study Completion: May 10, 2019
• Last Updated: February 24, 2021
• Results First Posted: February 24, 2021

Record last verified: 2021-02

Locations

US (1)