Individualized High Dose Methotrexate to Treat Cancer in Children Who Have a Significant Risk for Side Effects to Methotrexate
Condition: Cancer
Study type: Interventional

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.
    

Detailed description: 
      The study participant will receive the drug methotrexate as a patient in the hospital. High
      dose methotrexate will be given as a 24-hour infusion as part of the care determined to be
      necessary by their doctor. Infusion means the drug is given using a needle or tubing inserted
      into a vein (also called IV).

      The standard of care in patients receiving high dose methotrexate is to give the entire dose
      of methotrexate, without adjustment, and to then check the concentration of methotrexate in
      the blood at the end of the infusion. Most patients will have a level of methotrexate in
      their blood which is good to treat cancer and keep side effects at a minimum. However, other
      patients have a level of methotrexate at the end of the 24-hour infusion which is very high
      and is thought to lead to an increase in side effects.

      In this study, investigators are testing a method of giving methotrexate which may reduce the
      chances that the level of methotrexate in the blood at the end of the infusion is too high.
      This will be done by checking the methotrexate level in the blood at two times during the
      24-hour infusion and reducing the dose of methotrexate being given if the levels are not
      thought to be in the correct range (the level is too high). Reducing the dose may result in
      the patient receiving a lower total dose of methotrexate than initially ordered. However, it
      may also result in a more preferred concentration of methotrexate in the blood at the end of
      the infusion.

      It is possible that in the past the patient's doctor may have chosen to reduce the amount of
      methotrexate given because the patient had side effects. In this study, all patients will
      start out receiving the standard dose of methotrexate. Therefore, by participating in this
      study, the amount of methotrexate ordered at the start of the infusion may be higher than
      what the patient received previously.

      Before and after the patient receives high dose methotrexate, the patient will receive IV
      fluids. In order to minimize side effects, methotrexate levels will also be closely monitored
      after the infusion and the patient will receive supportive medicines as needed. The patient
      will receive the drug Leucovorin (administered by mouth every 6 hours for minimum of 3
      doses). The monitoring and supportive care that the patient will receive at the end of the
      methotrexate infusion, the amount of IV fluids, and the dose or duration of Leucovorin
      received will be done based on standard guidelines and are not part of this study.

      After receiving the 24-hour high dose methotrexate, this individualized monitoring plan will
      end and management of the patient's methotrexate levels will continue according to standard
      guidelines.

      High dose methotrexate may be given to the patient multiple times at the discretion of their
      doctor. While on this study, the patient will receive methotrexate using the methods of this
      study (however, they will only have blood drawn one time for optional DNA testing). The
      patient, his/her parent, or the doctor may decide to withdraw the patient from this study at
      any time if they do not think that it is in the patient's best interest to continue to
      receive methotrexate in the manner being investigated in this study.

      STUDY RELATED TESTS AND PROCEDURES

      At study entry, the following will occur:

        -  The patient will have a physical exam

        -  Collection of blood samples for routine blood tests and research blood tests.
           Approximately 1-2 teaspoons of blood will be taken for research blood tests.

        -  Review of the patient's medical and medication history to collect information.

      During treatment and after treatment the following will occur:

        -  Collection of blood samples for routine blood tests and research blood tests.
           Approximately ½ teaspoon of blood will be taken at times 2, 6 (or 8), 24, 36, 42, and 48
           hours. The blood collected at 2 and 6 (or 8) and 24 hours is for the research blood
           tests.

        -  Review of the patient's medical and medication history to collect information.

      The research blood tests are done to see how much methotrexate is in the body, how the body
      handles the drug, and to do DNA studies. The DNA will be tested to look for small changes
      called Single Nucleotide Polymorphisms (SNP). These small changes sometimes explain why
      different people have different reactions to drugs. The total amount of blood drawn for the
      research studies is approximately 3 teaspoons.
    

Intervention name(s): Methotrexate
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Methotrexate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cancer; High Dose Methotrexate