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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02076997
Recruitment Status : Completed
First Posted : March 4, 2014
Results First Posted : February 24, 2021
Last Update Posted : February 24, 2021
Sponsor:
Collaborator:
Texas Children's Cancer Center
Information provided by (Responsible Party):
Jennifer Foster, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Cancer Drug: Methotrexate Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Individualized High Dose Methotrexate for the Treatment of Malignancies in Children and Adolescents With a Significant Risk for Methotrexate Toxicities
Actual Study Start Date : January 1, 2014
Actual Primary Completion Date : May 30, 2017
Actual Study Completion Date : May 10, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Individualized High Dose Methotrexate
Individualized high dose methotrexate given as a 24-hour infusion.
Drug: Methotrexate

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.





Primary Outcome Measures :
  1. Incidence of Success (Achieving an End Infusion Peripheral Blood Methotrexate Concentration Between 50-80 μM) [ Time Frame: 1 month ]
    1a) Calculate the incidence of success with the new protocol (achieving an end infusion peripheral blood methotrexate concentration between 50-80 μM)


Secondary Outcome Measures :
  1. Incidence of >Grade 3 Nephrotoxicity [ Time Frame: 2.5 months ]
    Calculate the incidence of >grade 3 nephrotoxicity

  2. Incidence of Neurotoxicity [ Time Frame: 2.5 months ]
    Calculate the incidence of neurotoxicity

  3. Incidence of Mucositis [ Time Frame: 2.5 months ]
    Calculate the incidence of mucositis

  4. Incidence of Hepatoxicity [ Time Frame: 2.5 months ]
    Calculate the incidence of hepatotoxicity

  5. Incidence of Myelosuppression [ Time Frame: 2.5 months ]
    grade >/= 3 hematological toxicity


Other Outcome Measures:
  1. Description of the Genotype of Various Methotrexate Metabolizing SNPs [ Time Frame: 4 weeks ]
    We described the genotype of various identified methotrexate metabolizing SNPs

  2. Examination of Predictors of Success in Achieving Goal Concentration of Methotrexate [ Time Frame: 4 weeks ]
    We examined the predictors of success in achieving goal concentration of methotrexate



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02076997


Locations
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United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Cancer Center
Investigators
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Principal Investigator: Jennifer H Foster, MD Baylor College of Medicine
  Study Documents (Full-Text)

Documents provided by Jennifer Foster, Baylor College of Medicine:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Jennifer Foster, Assistant Professor of Pediatrics, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02076997    
Other Study ID Numbers: H-33119
First Posted: March 4, 2014    Key Record Dates
Results First Posted: February 24, 2021
Last Update Posted: February 24, 2021
Last Verified: February 2021
Keywords provided by Jennifer Foster, Baylor College of Medicine:
Cancer
High Dose Methotrexate
Additional relevant MeSH terms:
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Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors