Trial Outcomes & Findings for Individualized High Dose Methotrexate to Treat Cancer in Children Who Have a Significant Risk for Side Effects to Methotrexate (NCT NCT02076997)

Results Overview

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

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

23 participants

Primary outcome timeframe

1 month

Results posted on

2021-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	Individualized High Dose Methotrexate Individualized high dose methotrexate given as a 24-hour infusion. 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.
Overall Study STARTED	23
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Individualized High Dose Methotrexate n=22 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Age, Continuous	13 years n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	13 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Region of Enrollment United States	22 Participants n=93 Participants

PRIMARY outcome

Timeframe: 1 month

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

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=22 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of Success (Achieving an End Infusion Peripheral Blood Methotrexate Concentration Between 50-80 μM)	57 uM Standard Deviation 14

SECONDARY outcome

Timeframe: 2.5 months

Population: 22 patients were enrolled for a total of 54 cycles of methotrexate. Toxicities were recorded by cycle

Calculate the incidence of \>grade 3 nephrotoxicity

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=54 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of >Grade 3 Nephrotoxicity	0 Participants

SECONDARY outcome

Timeframe: 2.5 months

Population: 22 patients were enrolled for a total of 54 cycles of methotrexate. Toxicities were recorded by cycle

Calculate the incidence of neurotoxicity

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=54 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of Neurotoxicity	1 Participants

SECONDARY outcome

Timeframe: 2.5 months

Population: 22 patients were enrolled for a total of 54 cycles of methotrexate. Toxicities were recorded by cycle

Calculate the incidence of mucositis

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=54 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of Mucositis	5 Participants

SECONDARY outcome

Timeframe: 2.5 months

Population: total infusions

Calculate the incidence of hepatotoxicity

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=54 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of Hepatoxicity	10 infusions

SECONDARY outcome

Timeframe: 2.5 months

Population: 22 patients were enrolled for a total of 54 cycles of methotrexate. Toxicities were recorded by cycle

grade \>/= 3 hematological toxicity

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=54 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Incidence of Myelosuppression	39 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: The SNP analysis was descriptive data

We described the genotype of various identified methotrexate metabolizing SNPs

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=22 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Description of the Genotype of Various Methotrexate Metabolizing SNPs rs1801394	26 percent SNPs in the population
Description of the Genotype of Various Methotrexate Metabolizing SNPs rs1801133	36 percent SNPs in the population
Description of the Genotype of Various Methotrexate Metabolizing SNPs rs1801131	29 percent SNPs in the population
Description of the Genotype of Various Methotrexate Metabolizing SNPs rs7317112	43 percent SNPs in the population
Description of the Genotype of Various Methotrexate Metabolizing SNPs rs4149056	38 percent SNPs in the population

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks

Population: Among subjects who required at least one dose adjustment on study (n = 14), those who carried one or two copies of the minor allele of the C677T methylenetetrahydrofolate reductase (MTHFR) gene had an OR 6.7 (95% CI 0.49-91.3) of achieving success as defined by the protocol

We examined the predictors of success in achieving goal concentration of methotrexate

Outcome measures

Outcome measures
Measure	Individualized High Dose Methotrexate n=14 Participants Individualized high dose methotrexate given as a 24-hour infusion. 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.
Examination of Predictors of Success in Achieving Goal Concentration of Methotrexate	6.7 Odds Ratio Interval 0.49 to 91.3

Adverse Events

Individualized High Dose Methotrexate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Jennifer Foster

Baylor College of Medicine

Phone: 832-824-4646

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place