CancerNCT02076997
Individualized High Dose Methotrexate to Treat Cancer in Children Who Have a Significant Risk for Side Effects to Methotrexate
A study testing Methotrexate in people with Cancer, run by Baylor College of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 22 years
- Conditions the study is for
- Cancer
- What is being tested?
- Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2014to 10 May 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Individualized High Dose Methotrexate for the Treatment of Malignancies in Children and Adolescents With a Significant Risk for Methotrexate Toxicities
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.
Read more
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.
Read the 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.
- Conditions
- Cancer
- Being tested
- Methotrexate
- Keywords
- Cancer, High Dose Methotrexate
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Individualized High Dose Methotrexate | Experimental | Individualized high dose methotrexate given as a 24-hour infusion. Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 1 month
Secondary outcomes (5)
Incidence of >Grade 3 Nephrotoxicity
Calculate the incidence of >grade 3 nephrotoxicity
Measured: 2.5 months
Incidence of Neurotoxicity
Calculate the incidence of neurotoxicity
Measured: 2.5 months
Incidence of Mucositis
Calculate the incidence of mucositis
Measured: 2.5 months
Incidence of Hepatoxicity
Calculate the incidence of hepatotoxicity
Measured: 2.5 months
Incidence of Myelosuppression
grade >/= 3 hematological toxicity
Measured: 2.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study start1 Jan 2014
- Primary completion30 May 2017
- Study completion10 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Children's Cancer Center
- Responsible party
- Principal investigator, Jennifer Foster, Baylor College of Medicine
- Investigators
- Jennifer H Foster, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02076997
- Sponsor's protocol ID
- H-33119
- Status last verified
- Feb 2021
- First submitted
- 28 Feb 2014
- Last updated
- 24 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30488179
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized High Dose Methotrexate for the Treatment of Malignancies in Children and Adolescents With a Significant Risk for Methotrexate Toxicities
- ClinicalTrials.gov ID
- NCT02076997
- Acronym / sponsor ID
- H-33119
- Conditions
- Cancer
- Keywords
- Cancer, High Dose Methotrexate
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Texas Children's Cancer Center
- Study start
- 1 Jan 2014 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 10 May 2019 (actual)
- First posted
- 4 Mar 2014 (estimated)
- Results
- Posted 24 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individualized High Dose Methotrexate | Experimental | Drug: MethotrexateIndividualized high dose methotrexate given as a 24-hour infusion. |
Who may qualify
- Ages
- 1 year to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Individualized High Dose Methotrexate |
Primary outcome
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)
5 secondary outcomes
Incidence of >Grade 3 Nephrotoxicity
Time frame: 2.5 months
Incidence of Neurotoxicity
Time frame: 2.5 months
Incidence of Mucositis
Time frame: 2.5 months
Incidence of Hepatoxicity
Time frame: 2.5 months
Incidence of Myelosuppression
Time frame: 2.5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30488179Foster 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer H Foster, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methotrexate in people with Cancer, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Success (Achieving an End Infusion Peripheral Blood Methotrexate Concentration Between 50-80 μM) (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02076997, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2021.