Trial Outcomes & Findings for Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma (NCT NCT00602667)
NCT ID: NCT00602667
Last Updated: 2026-01-13
Results Overview
Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
293 participants
Primary outcome timeframe
From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment
Results posted on
2026-01-13
Participant Flow
293 participants were enrolled between December 17, 2007 and April 19, 2017.
Of the 293 participants enrolled, 3 were ineligible and removed from study, leaving 290 eligible patients. Eighty-one (81) of the 290 eligible patients enrolled had histologically confirmed medulloblastoma; medulloblastoma patients are the focus of the primary study objectives.
Participant milestones
| Measure |
Low-Risk Group
Patients with gross total resection (GTR)/no evidence of metastatic (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
|
Intermediate-Risk Group
Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy.
|
|---|---|---|---|
|
Overall Study
STARTED
|
57
|
156
|
77
|
|
Overall Study
COMPLETED
|
38
|
75
|
14
|
|
Overall Study
NOT COMPLETED
|
19
|
81
|
63
|
Reasons for withdrawal
| Measure |
Low-Risk Group
Patients with gross total resection (GTR)/no evidence of metastatic (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
|
Intermediate-Risk Group
Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy.
|
|---|---|---|---|
|
Overall Study
Still on Therapy
|
0
|
2
|
2
|
|
Overall Study
Death
|
0
|
1
|
1
|
|
Overall Study
Family request
|
3
|
25
|
6
|
|
Overall Study
Excessive toxicity
|
1
|
1
|
0
|
|
Overall Study
Second malignancy
|
0
|
1
|
0
|
|
Overall Study
Physician Decision
|
2
|
3
|
8
|
|
Overall Study
Progressive disease
|
13
|
48
|
45
|
|
Overall Study
Progressive disease prior to therapy
|
0
|
0
|
1
|
Baseline Characteristics
Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma
Baseline characteristics by cohort
| Measure |
Low-Risk Group
n=57 Participants
Patients with gross total resection (GTR)/no evidence of metastatic (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
|
Intermediate-Risk Group
n=156 Participants
Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.
|
High-Risk Group
n=77 Participants
Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy.
|
Total
n=290 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
16.1 months
n=210 Participants
|
21.9 months
n=19 Participants
|
20.0 months
n=123 Participants
|
20.1 months
n=123 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=210 Participants
|
66 Participants
n=19 Participants
|
43 Participants
n=123 Participants
|
131 Participants
n=123 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=210 Participants
|
90 Participants
n=19 Participants
|
34 Participants
n=123 Participants
|
159 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Mexican/Chicano
|
0 Participants
n=210 Participants
|
5 Participants
n=19 Participants
|
2 Participants
n=123 Participants
|
7 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · NOS Spanish, Hispanic, Latino
|
7 Participants
n=210 Participants
|
16 Participants
n=19 Participants
|
7 Participants
n=123 Participants
|
30 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Non Spanish speaking, Non Hispanic
|
47 Participants
n=210 Participants
|
120 Participants
n=19 Participants
|
64 Participants
n=123 Participants
|
231 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Puerto Rican
|
1 Participants
n=210 Participants
|
2 Participants
n=19 Participants
|
1 Participants
n=123 Participants
|
4 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · South or Central American
|
0 Participants
n=210 Participants
|
2 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
2 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Unknown
|
2 Participants
n=210 Participants
|
11 Participants
n=19 Participants
|
3 Participants
n=123 Participants
|
16 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian/Alaskan/White
|
1 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
1 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian/Alaskan Native
|
0 Participants
n=210 Participants
|
1 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
1 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
3 Participants
n=210 Participants
|
6 Participants
n=19 Participants
|
1 Participants
n=123 Participants
|
10 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Asian and White
|
0 Participants
n=210 Participants
|
2 Participants
n=19 Participants
|
2 Participants
n=123 Participants
|
4 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Black
|
6 Participants
n=210 Participants
|
14 Participants
n=19 Participants
|
10 Participants
n=123 Participants
|
30 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Black and White
|
0 Participants
n=210 Participants
|
1 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
1 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Multiple Race (NOS)
|
1 Participants
n=210 Participants
|
7 Participants
n=19 Participants
|
1 Participants
n=123 Participants
|
9 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Other
|
2 Participants
n=210 Participants
|
4 Participants
n=19 Participants
|
1 Participants
n=123 Participants
|
7 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Pacific Islander
|
1 Participants
n=210 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=123 Participants
|
1 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · Unknown
|
2 Participants
n=210 Participants
|
3 Participants
n=19 Participants
|
1 Participants
n=123 Participants
|
6 Participants
n=123 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
41 Participants
n=210 Participants
|
118 Participants
n=19 Participants
|
61 Participants
n=123 Participants
|
220 Participants
n=123 Participants
|
PRIMARY outcome
Timeframe: From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatmentPopulation: All eligible medulloblastoma patients started methotrexate and were included (n=81). PFS estimates are reported by risk group.
Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients
|
46.9 Percent Probability
Interval 30.2 to 63.6
|
30.8 Percent Probability
Interval 14.1 to 47.5
|
73.9 Percent Probability
Interval 56.5 to 91.3
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatmentPopulation: Eligible patients with molecularly confirmed medulloblastoma (n=76) were included. PFS estimates are reported by methylation subgroup and risk group. There were no low-risk group 3 or group 4 patients.
Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile.
Outcome measures
| Measure |
Intermediate-Risk Group
n=8 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=11 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
n=13 Participants
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
n=11 Participants
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
n=8 Participants
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
n=2 Participants
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup
|
50.0 Percent Probability
Interval 19.0 to 81.0
|
54.5 Percent Probability
Interval 27.3 to 81.7
|
73.9 Percent Probability
Interval 56.5 to 91.3
|
—
|
30.8 Percent Probability
Interval 8.5 to 53.1
|
9.1 Percent Probability
Interval 0.0 to 21.1
|
—
|
62.5 Percent Probability
Interval 31.9 to 93.1
|
50.0 Percent Probability
Interval 1.0 to 99.0
|
PRIMARY outcome
Timeframe: From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year afterPopulation: Eligible medulloblastoma patients (n=81) were included. EFS estimates are reported by risk group.
Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients
|
46.9 Percent Probability
Interval 30.2 to 63.6
|
30.8 Percent Probability
Interval 14.1 to 47.5
|
73.9 Percent Probability
Interval 56.5 to 91.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatmentPopulation: Eligible medulloblastoma patients (n=81) were included in these analyses. 23 of 23 low risk patients had data available for this objective, as did 27/32 and 24/26 intermediate and high risk patients.
Amplifications and deletions (gains and losses) for chromosomes of interest are shown in the table of measured values.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Chromosomal Abnormalities
chr6q gain/amplification
|
3 Participants
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr6q loss/deletion
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr8p gain/amplification
|
2 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr8p loss/deletion
|
6 Participants
|
8 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr8q gain/amplification
|
3 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr8q loss/deletion
|
5 Participants
|
7 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr9p gain/amplification
|
6 Participants
|
3 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr9p loss/deletion
|
0 Participants
|
3 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr9q gain/amplification
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr9q loss/deletion
|
5 Participants
|
5 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr10p gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr10p loss/deletion
|
5 Participants
|
7 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr10q gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr10q loss/deletion
|
7 Participants
|
9 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr20p gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr20p loss/deletion
|
4 Participants
|
5 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr20q gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr20q loss/deletion
|
3 Participants
|
5 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr2p gain/amplification
|
1 Participants
|
6 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr2p loss/deletion
|
2 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr2q gain/amplification
|
1 Participants
|
6 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr2q loss/deletion
|
2 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr6p gain/amplification
|
3 Participants
|
3 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Chromosomal Abnormalities
chr6p loss/deletion
|
0 Participants
|
2 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatmentPopulation: Eligible medulloblastoma patients (n=81) were included in these analyses. Not all patients had data available for each gene.
Gene alterations, which include single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations are shown for specific genes of interest in the results table.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Numbers of Patients With Gene Alterations
SUFU alteration
|
1 Participants
|
1 Participants
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
KMT2D alteration
|
1 Participants
|
3 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
SMO alteration
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
BCOR alteration
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
PTEN alteration
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
BRCA2 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
GLI2 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
SMARCA4 alteration
|
1 Participants
|
0 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
TP53 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
MYCN alteration
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Numbers of Patients With Gene Alterations
PTCH1 alteration
|
4 Participants
|
3 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatmentPopulation: Eligible patients with molecularly confirmed medulloblastoma (n=76) were included in these analyses. Not all patients had data available for each gene.
Alterations included single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations. Cytogenetic information shows gains and losses as specified in the table of measured values.
Outcome measures
| Measure |
Intermediate-Risk Group
n=8 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=11 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
n=13 Participants
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
n=11 Participants
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
n=8 Participants
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
n=2 Participants
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
SMO alteration
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
BCOR alteration
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
PTEN alteration
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
GLI2 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
SMARCA4 alteration
|
0 Participants
|
0 Participants
|
2 Participants
|
—
|
1 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
MYCN amplification
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr2p gain/amplification
|
0 Participants
|
4 Participants
|
5 Participants
|
—
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr2p loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr2q gain/amplification
|
0 Participants
|
4 Participants
|
5 Participants
|
—
|
0 Participants
|
1 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr2q loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr6p gain/amplification
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
2 Participants
|
3 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr6p loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
2 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr6q gain/amplification
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
2 Participants
|
3 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr6q loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
2 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr8p gain/amplification
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
1 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr8p loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
2 Participants
|
7 Participants
|
—
|
4 Participants
|
1 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr8q gain/amplification
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
2 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr8q loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
6 Participants
|
—
|
4 Participants
|
1 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr9p gain/amplification
|
4 Participants
|
3 Participants
|
4 Participants
|
—
|
1 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr9p loss/deletion
|
0 Participants
|
0 Participants
|
4 Participants
|
—
|
0 Participants
|
3 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr9q gain/amplification
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
1 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr9q loss/deletion
|
5 Participants
|
2 Participants
|
6 Participants
|
—
|
0 Participants
|
3 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr10p gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr10p loss/deletion
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
5 Participants
|
7 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr10q gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr10q loss/deletion
|
2 Participants
|
1 Participants
|
3 Participants
|
—
|
5 Participants
|
8 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr20p gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr20p loss/deletion
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
3 Participants
|
4 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr20q gain/amplification
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
chr20q loss/deletion
|
0 Participants
|
1 Participants
|
1 Participants
|
—
|
3 Participants
|
4 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
PTCH1 alteration
|
4 Participants
|
3 Participants
|
7 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
SUFU alteration
|
1 Participants
|
1 Participants
|
6 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
KMT2D alteration
|
1 Participants
|
3 Participants
|
5 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
BRCA2 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
|
Numbers of Patients With Molecular Abnormalities by Tumor Type
TP53 alteration
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatmentPopulation: All eligible patients enrolled (n=290) were included in this analysis. The numbers of patients with pre-study samples were considered for these results.
Successful collections will be defined as the number of patients who have frozen/fixed tumor samples available.
Outcome measures
| Measure |
Intermediate-Risk Group
n=156 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=77 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=57 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Successful Collections for Frozen and Fixed Tumor Samples
Number with frozen tumor tissue
|
73 Participants
|
32 Participants
|
27 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Successful Collections for Frozen and Fixed Tumor Samples
Number with fixed tumor tissue
|
153 Participants
|
71 Participants
|
54 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 yearsPopulation: Eligible medulloblastoma patients who received any methotrexate were included in this analysis. Hazard ratios with 95% confidence intervals are reported and compare SJYC07 patients to historical controls in each risk group. As there were too few low-risk historical controls, no hazard ratio is included for the low-risk group.
EFS was measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure. 1-year EFS estimates are reported by risk group. EFS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Event-free Survival (EFS) Compared to Historical Controls
|
46.9 Percent probability
Interval 30.2 to 63.6
|
30.8 Percent probability
Interval 14.1 to 47.5
|
73.9 Percent probability
Interval 56.5 to 91.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year after treatment initiation of last patientPopulation: Eligible medulloblastoma patients who received any methotrexate were included in this analysis. Hazard ratios with 95% confidence intervals are reported and compare SJYC07 patients to historical controls in each risk group. As there were too few low-risk historical controls, no hazard ratio is included for the low-risk group.
OS was measured from the date of initial treatment to date of death or to date of last contact for survivors. 1-year OS estimates were reported by risk group. OS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals.
Outcome measures
| Measure |
Intermediate-Risk Group
n=32 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=26 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival (OS) Compared to Historical Controls
|
84.4 Percent probability
Interval 72.1 to 96.7
|
61.5 Percent probability
Interval 43.9 to 79.1
|
100 Percent probability
Interval 100.0 to 100.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From on-study date to 2 months after completion of induction chemotherapy (up to 4 months after on-study date)Population: Eligible intermediate and high risk group patients who received at least 1 dose of methotrexate were included in this analysis. One of the high risk patients did not start therapy and was excluded.
For patients treated in the intermediate and high risk strata with residual or metastatic disease we will estimate the stratum-specific objective response rate (complete response (CR) or partial response \[ PR\]). All patients who receive at least 1 -dose of methotrexate are evaluable for response. Objective responses must be sustained for at least eight weeks.
Outcome measures
| Measure |
Intermediate-Risk Group
n=76 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=156 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percentage of Patients With Objective Responses Rate to Induction Chemotherapy
|
21.1 Percentage of patients
Interval 12.5 to 31.8
|
—
|
58.3 Percentage of patients
Interval 50.2 to 66.2
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From on-study date up to 4 months after on-study datePopulation: Eligible high-risk group patients who started therapy were included in this analysis (n=76). 1 patient enrolled on the high-risk arm did not start therapy due to early disease progression and was excluded. Courses 2-4 of induction and the 1st consolidation course were used in this analysis. 76 patients (with 263 courses) were included.
For the subset of patients with metastatic disease (high-risk group patients), during induction, the proportion percentage of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity will be calculated. Patients were to receive 4 courses of induction and then consolidation chemotherapy.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=263 courses
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
|
—
|
—
|
3.8 Percentage of courses delayed
Interval 1.8 to 6.9
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At completion of consolidation therapy (up to 6 months after on-study date)Population: Eligible high-risk group patients who started therapy were included. Course 2 of consolidation and the 1st course of maintenance were used in this analysis and assessed for delays \>7 days due to toxicity. Of the 76 high-risk patients that started induction therapy, 50 started consolidation (with 47 courses included in this analysis).
For the subset of patients with metastatic disease (high-risk group patients), during consolidation, we will calculate the number and proportion of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity. Patients were to received 2 courses of consolidation chemotherapy and then maintenance therapy.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=47 courses
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
|
—
|
—
|
2.6 Percentage of courses delayed
Interval 0.5 to 8.5
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 8 weeks after completion of consolidation therapy (up to 8 months after on-study date)Population: Of the 50 high-risk patients that started consolidation chemotherapy, 38 had measurable residual disease after induction and were included in this result.
For patients enrolled on the high-risk arm with measurable residual disease after induction treated with consolidation therapy, we will estimate the objective response (complete response (CR)/partial response (PR)) rate after consolidation therapy with a 95% confidence interval. Objective responses must be sustained for at least eight weeks. All patients who receive at least 1 dose of cyclophosphamide or topotecan during consolidation are evaluable for response.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percent of Patients With Sustained Objective Responses Rate After Consolidation
|
—
|
—
|
13.2 percentage of participants
Interval 4.4 to 28.1
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start of oral maintenance therapy (approximately 6 months after on-study date) to completion of oral maintenance therapy (up to 1 year after on-study date)Population: Eligible patients less than 3 years of age (n=273) constituted the study population for this analysis; 167 of these patients started the first course of maintenance and were included in this analysis (50 low-risk, 87 intermediate-risk, and 30 high-risk patients).
These data are based on patient diaries. For children \<3 years of age, we will calculate the percentage of total scheduled doses each patient received per course for each of the oral maintenance courses and report the overall average number percentage of doses received per course across patients. If patients received all planned doses, their percentage would be 100%. If the average percentage was less than 75%, then feasibility would be in question.
Outcome measures
| Measure |
Intermediate-Risk Group
n=87 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=30 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=50 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received
|
91 Percentage of scheduled doses received
Standard Deviation 23
|
98 Percentage of scheduled doses received
Standard Deviation 4
|
96 Percentage of scheduled doses received
Standard Deviation 8
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 3 times during RT consolidationPopulation: Intermediate risk patients treated at St. Jude were eligible to receive proton beam therapy through referral to the University of Florida Proton Therapy Institute. Patients electing to receive PBT and post-treatment PET scans after the delivery of one treatment beam were included in the analysis.
Measures will be analyzed for intermediate risk participants who receive proton beam therapy (PBT) and who consent. This objective aims to assess the feasibility of using post-proton beam therapy (PBT) positron emission tomography (PET) as an in-vivo dosimetric and distal edge verification system in this patient population. To quantify the decay in signal, 134 scans from 53 patients were analyzed by recording the mean activation value (MAV), the average recorded PET signal from activation, within the target volume. With each patient being given the same dose, the percent standard deviation in the MAV can serve as a quantitative representation of signal loss due to radioactive decay.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=134 Scans
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Percent of PET Scans With Loss of Signal Intensity
|
—
|
—
|
60 mean activation value (MAV)
Standard Deviation 27
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, at the completion of therapy, and every 12 months up to 36 months after off therapy datePopulation: Eligible patients who had cerebrospinal fluid neurotransmitter studies performed. Seventeen patients had studies performed.
Concentrations of various neurotransmitters in cerebrospinal fluid were measured at 5 timepoints. The median concentration of each neurotransmitter at each time point was calculated and provided with a full range.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=17 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
3,4-dihydroxyphenylacetic acid concentration at completion of treatment
|
—
|
—
|
1.62 ng/ml
Interval 0.82 to 9.91
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
3,4-dihydroxyphenylacetic acid concentration at 12 months off treatment
|
—
|
—
|
1.04 ng/ml
Interval 0.51 to 6.55
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
3,4-dihydroxyphenylacetic acid concentration at 24 months off treatment
|
—
|
—
|
1.52 ng/ml
Interval 0.31 to 6.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
3,4-dihydroxyphenylacetic acid concentration at 36 months off treatment
|
—
|
—
|
1.00 ng/ml
Interval 0.38 to 3.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxytryptamine concentration at baseline
|
—
|
—
|
2.38 ng/ml
Interval 0.12 to 13.94
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxytryptamine concentration at completion of treatment
|
—
|
—
|
2.01 ng/ml
Interval 0.06 to 15.01
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxytryptamine concentration at 12 months off treatment
|
—
|
—
|
2.00 ng/ml
Interval 0.06 to 8.46
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxytryptamine concentration at 24 months off treatment
|
—
|
—
|
2.44 ng/ml
Interval 1.01 to 7.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxytryptamine concentration at 36 months off treatment
|
—
|
—
|
1.62 ng/ml
Interval 0.29 to 8.85
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxyindoleacetic acid concentration at baseline
|
—
|
—
|
52.03 ng/ml
Interval 30.02 to 400.35
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxyindoleacetic acid concentration at completion of treatment
|
—
|
—
|
52.72 ng/ml
Interval 27.42 to 110.24
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxyindoleacetic acid concentration at 12 months off treatment
|
—
|
—
|
35.72 ng/ml
Interval 24.58 to 51.6
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxyindoleacetic acid concentration at 24 months off treatment
|
—
|
—
|
33.98 ng/ml
Interval 25.69 to 45.63
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Hydroxyindoleacetic acid concentration at 36 months off treatment
|
—
|
—
|
31.56 ng/ml
Interval 16.09 to 53.04
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Homovanillic acid concentration at baseline
|
—
|
—
|
82.44 ng/ml
Interval 34.57 to 565.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Homovanillic acid concentration at completion of treatment
|
—
|
—
|
114.13 ng/ml
Interval 73.43 to 179.21
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Homovanillic acid concentration at 12 months off treatment
|
—
|
—
|
68.28 ng/ml
Interval 40.78 to 146.84
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Homovanillic acid concentration at 24 months off treatment
|
—
|
—
|
88.27 ng/ml
Interval 55.27 to 166.99
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Homovanillic acid concentration at 36 months off treatment
|
—
|
—
|
79.78 ng/ml
Interval 35.4 to 152.51
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Dopamine concentration at baseline
|
—
|
—
|
3.16 ng/ml
Interval 0.18 to 4586.18
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Dopamine concentration at completion of treatment
|
—
|
—
|
3.70 ng/ml
Interval 0.82 to 39.16
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Dopamine concentration at 12 months off treatment
|
—
|
—
|
6.43 ng/ml
Interval 2.2 to 486.46
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Dopamine concentration at 24 months off treatment
|
—
|
—
|
4.46 ng/ml
Interval 0.04 to 1093.28
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
Dopamine concentration at 36 months off treatment
|
—
|
—
|
4.05 ng/ml
Interval 0.11 to 9.32
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Concentration of Cerebrospinal Fluid Neurotransmitters
3,4-dihydroxyphenylacetic acid concentration at baseline
|
—
|
—
|
2.56 ng/ml
Interval 0.91 to 11.24
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At study enrollment (Day 0)Population: Three genetic polymorphisms involved in dopamine metabolism (rs6323, rs4680, and rs6280) were studied in 17 patients with CNS neurotransmitter studies.
Types of genetic polymorphisms of neurotransmitters were examined. We studied 3 genetic polymorphisms; these were types of genetic polymorphisms involved in dopamine metabolism. They were as follows: rs6323, rs4680, and rs6280.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=17 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Number and Type of Genetic Polymorphisms
rs6323
|
—
|
—
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number and Type of Genetic Polymorphisms
rs4680
|
—
|
—
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number and Type of Genetic Polymorphisms
rs6280
|
—
|
—
|
17 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At study enrollment (Day 0)Population: Eligible patients who had neurotransmitter studies performed. Seventeen patients had studies performed.
Frequencies of genetic polymorphisms were reported.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=17 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · AA
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · AG
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · CC
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · GG
|
—
|
—
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · TC
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · TG
|
—
|
—
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs6323 · TT
|
—
|
—
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · AA
|
—
|
—
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · AG
|
—
|
—
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · CC
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · GG
|
—
|
—
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · TC
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · TG
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs4680 · TT
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · AA
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · AG
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · CC
|
—
|
—
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · GG
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · TC
|
—
|
—
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · TG
|
—
|
—
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacogenetic Variation on Central Nervous System Transmitters
Genetic Polymorphisms for dopamine receptor D (DRD3) rs6280 · TT
|
—
|
—
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapyPopulation: Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients.
Endocrine screening and growth hormone (GH) testing were done in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Endocrinopathy was defined as the presence of central hypothyroidism (free T4 concentration below normal with low or normal TSH concentration), growth hormone deficiency (peak growth hormone concentration below 5 ng/mL on dynamic testing), or ACTH deficiency (cortisol concentration below 14 ug/dL after low dose cosyntropin stimulation). Numbers of participants with endocrinopathy at each time point are reported. Please note the small numbers of participants with available data.
Outcome measures
| Measure |
Intermediate-Risk Group
n=24 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Endocrinopathy
End of induction-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
End of therapy-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
6-months off therapy-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
12-months off therapy-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
24-months off therapy-number with endocrinopathy
|
2 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
36-months off therapy-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
48-months off therapy-number with endocrinopathy
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Endocrinopathy
60-months off therapy-number with endocrinopathy
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: End of induction therapy (approximately 16 weeks from start of treatment), end of therapy (approximately 48 weeks from start of treatment), and 6, 12, 24, 36, 48, and 60 months off therapyPopulation: Growth hormone secretion was measured in consenting intermediate risk patients. No Intermediate Risk patients had data available at 12, 36, 48, and 60 months off therapy.
Growth hormone secretion was measured in consenting intermediate risk patients at the end of induction therapy, the end of all therapy, and at 6, 12, 24, 36, 48, and 60 months off therapy. Mean growth hormone secretion values are reported by assessment time point. Please note the small numbers of participants with available data.
Outcome measures
| Measure |
Intermediate-Risk Group
n=20 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Growth Hormone Secretion
24-months off therapy
|
9.2 ng/mL
Standard Deviation 6.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Growth Hormone Secretion
End of induction
|
15.3 ng/mL
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Growth Hormone Secretion
End of therapy
|
13.4 ng/mL
Standard Deviation 6.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Growth Hormone Secretion
6-months off therapy
|
7.3 ng/mL
Standard Deviation 2.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of Methotrexate (MTX)Population: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=94 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=44 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=37 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Clearance in Induction Cycle 1
|
6.06 L/h/m^2
Interval 3.07 to 10.69
|
5.65 L/h/m^2
Interval 1.71 to 9.45
|
5.69 L/h/m^2
Interval 2.19 to 11.08
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=93 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=41 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Clearance in Induction Cycle 2
|
5.70 L/h/m^2
Interval 2.71 to 8.98
|
5.70 L/h/m^2
Interval 2.78 to 8.79
|
5.47 L/h/m^2
Interval 2.43 to 10.56
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=82 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=36 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=35 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Clearance in Induction Cycle 3
|
5.78 L/h/m^2
Interval 2.59 to 9.27
|
5.81 L/h/m^2
Interval 2.78 to 10.2
|
5.68 L/h/m^2
Interval 1.93 to 9.61
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=80 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=34 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Clearance in Induction Cycle 4
|
5.89 L/h/m^2
Interval 2.95 to 8.84
|
5.79 L/h/m^2
Interval 2.36 to 9.16
|
5.75 L/h/m^2
Interval 2.14 to 9.65
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=94 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=44 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=37 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Volume of Central Compartment in Induction Cycle 1
|
13.70 L/m^2
Interval 7.03 to 28.21
|
13.25 L/m^2
Interval 5.65 to 20.89
|
11.63 L/m^2
Interval 7.09 to 29.58
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=93 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=41 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Volume of Central Compartment in Induction Cycle 2
|
13.73 L/m^2
Interval 6.47 to 31.45
|
13.62 L/m^2
Interval 6.87 to 22.39
|
13.77 L/m^2
Interval 5.88 to 28.19
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=82 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=36 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=35 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Volume of Central Compartment in Induction Cycle 3
|
13.55 L/m^2
Interval 7.31 to 24.48
|
13.87 L/m^2
Interval 6.84 to 22.88
|
12.70 L/m^2
Interval 6.27 to 28.9
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=94 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=44 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=37 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate AUC0-66h in Induction Cycle 1
|
1813 µmol·h/L
Interval 1029.0 to 3584.0
|
1821 µmol·h/L
Interval 1053.0 to 3631.0
|
1797 µmol·h/L
Interval 993.0 to 5029.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=93 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=41 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate AUC0-66h in Induction Cycle 2
|
1902 µmol·h/L
Interval 1225.0 to 3742.0
|
1879 µmol·h/L
Interval 1229.0 to 3271.0
|
1900 µmol·h/L
Interval 1042.0 to 3267.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=80 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=34 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Volume of Central Compartment in Induction Cycle 4
|
13.31 L/m^2
Interval 7.93 to 21.51
|
13.68 L/m^2
Interval 6.94 to 21.82
|
12.64 L/m^2
Interval 7.16 to 22.92
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=82 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=36 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=35 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate AUC0-66h in Induction Cycle 3
|
1879 µmol·h/L
Interval 1187.0 to 3756.0
|
1831 µmol·h/L
Interval 979.0 to 3139.0
|
1872 µmol·h/L
Interval 1145.0 to 3501.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=80 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=34 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate AUC0-66h in Induction Cycle 4
|
1841 µmol·h/L
Interval 1245.0 to 3727.0
|
1886 µmol·h/L
Interval 1219.0 to 3491.0
|
1804 µmol·h/L
Interval 1141.0 to 3504.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 42 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 1 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=93 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=44 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=37 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1
|
0.57 µmol/L
Interval 0.15 to 4.61
|
0.61 µmol/L
Interval 0.14 to 2.09
|
0.49 µmol/L
Interval 0.22 to 3.68
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 42 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 2 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=93 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=41 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2
|
0.72 µmol/L
Interval 0.26 to 7.61
|
0.69 µmol/L
Interval 0.24 to 1.49
|
0.75 µmol/L
Interval 0.19 to 3.09
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 42 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 3 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=82 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=36 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=35 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3
|
0.70 µmol/L
Interval 0.16 to 4.34
|
0.58 µmol/L
Interval 0.24 to 1.96
|
0.65 µmol/L
Interval 0.2 to 2.88
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 42 hours from start of MTXPopulation: Eligible patients who received methotrexate during induction cycle 4 and had samples collected for PK analysis.
Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=80 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=34 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4
|
0.64 µmol/L
Interval 0.22 to 3.22
|
0.55 µmol/L
Interval 0.2 to 1.79
|
0.64 µmol/L
Interval 0.26 to 3.12
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis..
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=91 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=42 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide Clearance in Induction Chemotherapy
|
2.23 L/h/m^2
Interval 1.23 to 8.95
|
2.25 L/h/m^2
Interval 0.84 to 3.4
|
2.40 L/h/m^2
Interval 1.16 to 9.15
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=4 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=28 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=20 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1
|
2.08 L/h/m^2
Interval 1.97 to 2.62
|
2.43 L/h/m^2
Interval 1.29 to 3.21
|
2.39 L/h/m^2
Interval 1.65 to 3.44
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=3 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=29 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2
|
2.55 L/h/m^2
Interval 2.19 to 2.93
|
2.37 L/h/m^2
Interval 1.61 to 3.16
|
2.48 L/h/m^2
Interval 1.97 to 3.35
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.75, 3 and 6 hours post-dosePopulation: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide apparent oral clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=42 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=26 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1
|
2.83 L/h/m^2
Interval 2.23 to 5.14
|
2.74 L/h/m^2
Interval 2.23 to 4.02
|
2.95 L/h/m^2
Interval 2.05 to 3.89
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=91 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=42 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide AUC0-24h in Induction Chemotherapy
|
2150 µmol·h/L
Interval 615.0 to 3430.0
|
2105 µmol·h/L
Interval 1523.0 to 5121.0
|
2070 µmol·h/L
Interval 592.0 to 4158.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=4 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=28 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=20 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
|
1504 µmol·h/L
Interval 617.0 to 2511.0
|
868 µmol·h/L
Interval 660.0 to 1498.0
|
1968 µmol·h/L
Interval 1480.0 to 2869.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=4 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=28 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=20 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
|
48.7 µmol·h/L
Interval 25.8 to 124.6
|
39.8 µmol·h/L
Interval 25.5 to 59.8
|
96.8 µmol·h/L
Interval 63.0 to 124.4
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=3 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=29 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
|
799 µmol·h/L
Interval 740.0 to 2303.0
|
899 µmol·h/L
Interval 700.0 to 1240.0
|
1966 µmol·h/L
Interval 1437.0 to 2519.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dosePopulation: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide AUC0-24h are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=42 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=26 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
|
38.7 µmol·h/L
Interval 21.2 to 54.9
|
42.2 µmol·h/L
Interval 28.0 to 53.0
|
39.9 µmol·h/L
Interval 25.3 to 51.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
4-OH cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=91 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=42 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy
|
111.3 µmol·h/L
Interval 71.4 to 181.0
|
109.1 µmol·h/L
Interval 65.0 to 175.0
|
116.4 µmol·h/L
Interval 74.6 to 200.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=3 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=29 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
|
49.5 µmol·h/L
Interval 39.5 to 84.5
|
43.5 µmol·h/L
Interval 30.8 to 72.5
|
95.9 µmol·h/L
Interval 81.7 to 131.1
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dosePopulation: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
4-OH cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=42 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=26 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
|
1.96 µmol·h/L
Interval 1.12 to 3.08
|
1.82 µmol·h/L
Interval 1.19 to 2.4
|
1.98 µmol·h/L
Interval 0.98 to 3.01
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during a cycle of induction therapy and had samples collected for PK analysis.
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 9 in one induction cycle. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=91 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=42 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=38 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
CEPM AUC0-24h in Induction Chemotherapy
|
137.8 µmol·h/L
Interval 80.4 to 328.9
|
135.3 µmol·h/L
Interval 57.6 to 591.7
|
140.2 µmol·h/L
Interval 50.1 to 453.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 1 and had samples collected for PK analysis.
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=4 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=28 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=20 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1
|
62.2 µmol·h/L
Interval 48.8 to 193.9
|
51.8 µmol·h/L
Interval 18.9 to 97.0
|
128.9 µmol·h/L
Interval 90.8 to 272.9
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusionPopulation: Eligible patients who received cyclophosphamide during consolidation cycle 2 and had samples collected for PK analysis.
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=3 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=29 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2
|
46.8 µmol·h/L
Interval 41.9 to 69.0
|
44.0 µmol·h/L
Interval 21.1 to 73.9
|
132.7 µmol·h/L
Interval 89.7 to 244.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dosePopulation: Eligible patients who received cyclophosphamide during maintenance cycle A1 and had samples collected for PK analysis.
Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=42 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=26 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1
|
1.65 µmol·h/L
Interval 0.68 to 3.64
|
1.41 µmol·h/L
Interval 0.64 to 3.96
|
1.59 µmol·h/L
Interval 0.75 to 3.48
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusionPopulation: Eligible patients who received topotecan with empirical dosage during consolidation therapy were included in this analysis. Per protocol, low-risk and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after an empiric dosage during consolidation phase of therapy are reported.
Outcome measures
| Measure |
Intermediate-Risk Group
n=27 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=1 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan
|
8 participants
|
—
|
0 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusionPopulation: Eligible patients who received topotecan with PK-guided dosage adjustment during consolidation therapy were included in this analysis. Per protocol, low-risk and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
Number of participants who successfully achieve target systemic exposure of intravenous topotecan after a pharmacokinetic-guided dosage adjustment during consolidation phase of therapy are reported.
Outcome measures
| Measure |
Intermediate-Risk Group
n=27 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=1 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan
|
20 participants
|
—
|
1 participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusionPopulation: Eligible patients who received intravenous topotecan during consolidation cycle 1 and had PK samples collected were included in this analysis. Per protocol, low- and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=27 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=1 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Topotecan Clearance in Consolidation Chemotherapy
|
26.40 L/h/m^2
Interval 6.8 to 43.0
|
—
|
30.3 L/h/m^2
Interval 30.3 to 30.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 1.5 and 6 hours post-dosePopulation: Eligible patients who received oral topotecan during maintenance therapy cycle A1 and had samples collected for PK analysis.
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan apparent oral clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=33 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=10 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Topotecan Apparent Oral Clearance in Maintenance Chemotherapy
|
41.0 L/h
Interval 24.4 to 62.7
|
44.6 L/h
Interval 18.1 to 57.0
|
41.4 L/h
Interval 12.3 to 54.6
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-infusion, 5 min., 1, 3, and 24 hours from end of infusionPopulation: Eligible patients who received intravenous topotecan during consolidation cycle 1 and had PK samples collected were included in this analysis. Per protocol, low- and intermediate-risk patients did not receive topotecan during consolidation unless they experienced disease progression during induction. One such intermediate-risk patient was included.
Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=27 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=1 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Topotecan AUC0-24h in Consolidation Chemotherapy
|
116 µg·h/L
Interval 90.0 to 262.0
|
—
|
117 µg·h/L
Interval 117.0 to 117.0
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 1.5, 6, and 24 hours post-dosePopulation: Eligible patients who received oral topotecan during maintenance therapy cycle A1 and had samples collected for PK analysis.
Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=33 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=10 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=18 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Topotecan AUC0-24h in Maintenance Chemotherapy
|
11.60 µg·h/L
Interval 7.93 to 20.5
|
10.33 µg·h/L
Interval 7.96 to 16.61
|
10.90 µg·h/L
Interval 9.04 to 24.36
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dosePopulation: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent oral clearance are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=11 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=3 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=10 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Erlotinib Apparent Oral Clearance
|
7.79 L/h/m^2
Interval 3.87 to 16.84
|
8.40 L/h/m^2
Interval 5.96 to 10.46
|
6.53 L/h/m^2
Interval 3.13 to 18.55
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dosePopulation: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent volume of central compartment are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=11 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=3 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=10 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Erlotinib Apparent Volume of Central Compartment
|
61.7 L/m^2
Interval 41.3 to 119.0
|
104.8 L/m^2
Interval 47.6 to 109.9
|
72.9 L/m^2
Interval 39.5 to 233.7
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dosePopulation: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=11 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=3 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=10 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Erlotinib AUC0-24h
|
23.5 µmol·h/L
Interval 12.5 to 48.6
|
22.0 µmol·h/L
Interval 13.8 to 33.0
|
31.0 µmol·h/L
Interval 7.2 to 64.8
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dosePopulation: Eligible patients who received oral erlotinib during maintenance therapy cycle B2 and had samples collected for PK analysis.
Erlotinib metabolite OSI-420 plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of OSI-420 AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis.
Outcome measures
| Measure |
Intermediate-Risk Group
n=11 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=3 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=10 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
OSI-420 AUC0-24h
|
1.81 µmol·h/L
Interval 1.17 to 6.97
|
1.62 µmol·h/L
Interval 1.25 to 2.93
|
2.17 µmol·h/L
Interval 0.73 to 5.98
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year after completion of radiation therapy for last patientPopulation: Eligible intermediate-risk patients who received focal radiation were included in this analysis. Of the 156 intermediate risk patients, 121 started radiation.
Local failure was defined as the interval from end of RT to date of local failure (or combined local + distant failure). Competing events were distant failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=121 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Rate of Local Disease Progression
|
—
|
—
|
13.2 Percentage of participants
Interval 7.2 to 19.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year after completion of radiation therapy for last patientPopulation: Eligible intermediate-risk patients who received focal radiation were included in this analysis. Of the 156 intermediate risk patients, 121 started radiation.
Distant failure was defined as the interval from end of RT to date of distant failure (or combined local + distant failure). Competing events were local failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval.
Outcome measures
| Measure |
Intermediate-Risk Group
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=121 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Rate of Distant Disease Progression
|
—
|
—
|
25.6 percentage of participants
Interval 17.8 to 33.4
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Global cognitive functioning was measured based on Cognitive Composite Scores from the Bayley III instrument for subjects \<3 years of age and on estimated IQ scores from the Stanford Binet V instrument for subjects ≥3 years of age. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Outcome measures
| Measure |
Intermediate-Risk Group
n=111 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=41 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=48 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
Baseline
|
91.0 score on a scale
Standard Deviation 15.4
|
87.4 score on a scale
Standard Deviation 22.3
|
88.6 score on a scale
Standard Deviation 17.6
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
Prior to Maintenance Therapy
|
92.3 score on a scale
Standard Deviation 15.1
|
94.8 score on a scale
Standard Deviation 19.0
|
91.1 score on a scale
Standard Deviation 16.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
36 Months Off Therapy
|
89.9 score on a scale
Standard Deviation 16.2
|
81.3 score on a scale
Standard Deviation 17.4
|
92.4 score on a scale
Standard Deviation 26.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
Completion of Therapy
|
93.4 score on a scale
Standard Deviation 15.3
|
76.8 score on a scale
Standard Deviation 18.6
|
85.8 score on a scale
Standard Deviation 17.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
12 Months Off Therapy
|
89.9 score on a scale
Standard Deviation 15.6
|
83.3 score on a scale
Standard Deviation 18.3
|
89.2 score on a scale
Standard Deviation 21.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
24 Months Off Therapy
|
89.4 score on a scale
Standard Deviation 19.0
|
77.7 score on a scale
Standard Deviation 21.0
|
97.6 score on a scale
Standard Deviation 16.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
48 Months Off Therapy
|
91.3 score on a scale
Standard Deviation 18.4
|
85.2 score on a scale
Standard Deviation 27.4
|
85.3 score on a scale
Standard Deviation 24.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Global Cognitive Functioning as Measured by Cognitive Composite Scores and Estimated IQ Scores
60 Months Off Therapy
|
85.3 score on a scale
Standard Deviation 17.9
|
71.5 score on a scale
Standard Deviation 18.4
|
82.0 score on a scale
Standard Deviation 25.6
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring attention were obtained from the Attention Problems T-score on the BASC-2 instrument which is a parent report. Higher scores indicate more attention problems. The normative mean is 50 with a standard deviation of 10.
Outcome measures
| Measure |
Intermediate-Risk Group
n=86 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=40 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
12 Months Off Therapy
|
53.9 score on a scale
Standard Deviation 10.2
|
53.9 score on a scale
Standard Deviation 13.0
|
56.2 score on a scale
Standard Deviation 10.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
60 Months Off Therapy
|
57.7 score on a scale
Standard Deviation 12.0
|
58.8 score on a scale
Standard Deviation 12.5
|
51.9 score on a scale
Standard Deviation 11.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
24 Months Off Therapy
|
55.3 score on a scale
Standard Deviation 10.1
|
49.8 score on a scale
Standard Deviation 12.6
|
54.5 score on a scale
Standard Deviation 10.6
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
36 Months Off Therapy
|
55.1 score on a scale
Standard Deviation 9.8
|
53.3 score on a scale
Standard Deviation 12.2
|
53.3 score on a scale
Standard Deviation 8.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
48 Months Off Therapy
|
55.5 score on a scale
Standard Deviation 10.1
|
55.3 score on a scale
Standard Deviation 10.3
|
56.4 score on a scale
Standard Deviation 10.4
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
Baseline
|
49.6 score on a scale
Standard Deviation 9.5
|
49.2 score on a scale
Standard Deviation 9.1
|
51.7 score on a scale
Standard Deviation 10.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
Prior to Maintenance Therapy
|
51.3 score on a scale
Standard Deviation 9.9
|
52.4 score on a scale
Standard Deviation 4.6
|
53.5 score on a scale
Standard Deviation 9.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Attention as Measured by Attention Problems T-scores
Completion of Therapy
|
50.9 score on a scale
Standard Deviation 9.4
|
43.3 score on a scale
Standard Deviation 12.7
|
52.6 score on a scale
Standard Deviation 8.6
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring processing speed were obtained based on the visual matching standard score from the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Outcome measures
| Measure |
Intermediate-Risk Group
n=49 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=9 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=23 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
Baseline
|
96.5 score on a scale
Standard Deviation 11.0
|
107.0 score on a scale
|
119.0 score on a scale
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
Completion of Therapy
|
100.2 score on a scale
Standard Deviation 15.2
|
—
|
105.3 score on a scale
Standard Deviation 20.2
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
Prior to Maintenance Therapy
|
97.6 score on a scale
Standard Deviation 12.3
|
109.5 score on a scale
Standard Deviation 2.1
|
89.0 score on a scale
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
12 Months Off Therapy
|
93.1 score on a scale
Standard Deviation 13.3
|
71.0 score on a scale
|
96.8 score on a scale
Standard Deviation 9.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
24 Months Off Therapy
|
90.2 score on a scale
Standard Deviation 15.3
|
89.3 score on a scale
Standard Deviation 13.3
|
98.4 score on a scale
Standard Deviation 16.6
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
36 Months Off Therapy
|
89.7 score on a scale
Standard Deviation 20.2
|
89.8 score on a scale
Standard Deviation 12.4
|
101.6 score on a scale
Standard Deviation 15.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
48 Months Off Therapy
|
87.6 score on a scale
Standard Deviation 14.7
|
78.7 score on a scale
Standard Deviation 17.0
|
93.2 score on a scale
Standard Deviation 23.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Processing Speed as Measured by Visual Matching Standard Scores
60 Months Off Therapy
|
84.6 score on a scale
Standard Deviation 17.1
|
65.0 score on a scale
|
86.3 score on a scale
Standard Deviation 36.2
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring executive functioning were obtained from Global Executive Composite (GEC) T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Outcome measures
| Measure |
Intermediate-Risk Group
n=85 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=40 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
60 Months Off Therapy
|
58.3 score on a scale
Standard Deviation 15.0
|
55.2 score on a scale
Standard Deviation 13.4
|
55.1 score on a scale
Standard Deviation 11.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
Baseline
|
49.6 score on a scale
Standard Deviation 9.7
|
52.4 score on a scale
Standard Deviation 13.1
|
59.2 score on a scale
Standard Deviation 16.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
Prior to Maintenance Therapy
|
52.5 score on a scale
Standard Deviation 12.3
|
49.3 score on a scale
Standard Deviation 11.9
|
54.3 score on a scale
Standard Deviation 9.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
Completion of Therapy
|
50.6 score on a scale
Standard Deviation 10.1
|
45.3 score on a scale
Standard Deviation 14.7
|
55.3 score on a scale
Standard Deviation 11.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
12 Months Off Therapy
|
56.5 score on a scale
Standard Deviation 14.3
|
60.1 score on a scale
Standard Deviation 20.0
|
57.9 score on a scale
Standard Deviation 13.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
24 Months Off Therapy
|
55.1 score on a scale
Standard Deviation 13.6
|
52.1 score on a scale
Standard Deviation 9.6
|
59.9 score on a scale
Standard Deviation 16.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
36 Months Off Therapy
|
57.7 score on a scale
Standard Deviation 11.8
|
58.2 score on a scale
Standard Deviation 11.1
|
55.7 score on a scale
Standard Deviation 12.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Executive Functioning as Measured by Global Executive Composite T-scores
48 Months Off Therapy
|
55.6 score on a scale
Standard Deviation 11.7
|
49.5 score on a scale
Standard Deviation 10.6
|
60.3 score on a scale
Standard Deviation 16.8
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring working memory were obtained from Working Memory T-scores, which were obtained from the Behavior Rating Inventory of Executive Function (BRIEF) instrument which is a parent report. Higher scores indicate more problems. The normative mean is 50 with a standard deviation of 10.
Outcome measures
| Measure |
Intermediate-Risk Group
n=85 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=34 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=40 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
Baseline
|
51.6 score on a scale
Standard Deviation 10.8
|
57.0 score on a scale
Standard Deviation 13.6
|
63.2 score on a scale
Standard Deviation 16.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
Prior to Maintenance Therapy
|
55.5 score on a scale
Standard Deviation 13.3
|
54.1 score on a scale
Standard Deviation 11.1
|
58.7 score on a scale
Standard Deviation 10.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
Completion of Therapy
|
54.9 score on a scale
Standard Deviation 11.1
|
49.0 score on a scale
Standard Deviation 16.8
|
60.8 score on a scale
Standard Deviation 14.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
12 Months Off Therapy
|
60.4 score on a scale
Standard Deviation 14.5
|
67.7 score on a scale
Standard Deviation 22.3
|
64.4 score on a scale
Standard Deviation 16.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
24 Months Off Therapy
|
59.4 score on a scale
Standard Deviation 14.7
|
55.4 score on a scale
Standard Deviation 13.3
|
63.6 score on a scale
Standard Deviation 17.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
36 Months Off Therapy
|
62.0 score on a scale
Standard Deviation 14.2
|
61.7 score on a scale
Standard Deviation 8.6
|
59.3 score on a scale
Standard Deviation 13.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
48 Months Off Therapy
|
60.0 score on a scale
Standard Deviation 13.1
|
54.5 score on a scale
Standard Deviation 12.8
|
60.9 score on a scale
Standard Deviation 16.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Working Memory as Measured by Working Memory T-scores
60 Months Off Therapy
|
60.6 score on a scale
Standard Deviation 14.3
|
61.0 score on a scale
Standard Deviation 15.3
|
56.8 score on a scale
Standard Deviation 13.3
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring verbal fluency were obtained from Retrieval Fluency standard scores on the Woodcock Johnson III instrument. Higher scores indicate better performance. The normative mean is 100 with a standard deviation of 15.
Outcome measures
| Measure |
Intermediate-Risk Group
n=50 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=10 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=25 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
Baseline
|
87.7 score on a scale
Standard Deviation 18.4
|
—
|
117.0 score on a scale
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
Prior to Maintenance Therapy
|
89.4 score on a scale
Standard Deviation 13.4
|
—
|
97.0 score on a scale
Standard Deviation 5.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
Completion of Therapy
|
95.3 score on a scale
Standard Deviation 14.4
|
—
|
90.0 score on a scale
Standard Deviation 13.2
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
12 Months Off Therapy
|
86.1 score on a scale
Standard Deviation 19.9
|
87.0 score on a scale
Standard Deviation 1.4
|
94.8 score on a scale
Standard Deviation 11.4
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
24 Months Off Therapy
|
82.5 score on a scale
Standard Deviation 20.6
|
90.8 score on a scale
Standard Deviation 4.6
|
98.8 score on a scale
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
36 Months Off Therapy
|
88.1 score on a scale
Standard Deviation 24.9
|
81.4 score on a scale
Standard Deviation 14.9
|
100.2 score on a scale
Standard Deviation 13.3
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
48 Months Off Therapy
|
88.7 score on a scale
Standard Deviation 16.0
|
95.7 score on a scale
Standard Deviation 15.0
|
77.1 score on a scale
Standard Deviation 16.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Verbal Fluency as Measured by Retrieval Fluency Standard Scores
60 Months Off Therapy
|
87.9 score on a scale
Standard Deviation 16.4
|
70.3 score on a scale
Standard Deviation 23.7
|
81.9 score on a scale
Standard Deviation 22.1
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring visual-spatial reasoning were obtained from VMI T-scores on the Beery VMI instrument. Higher scores indicate better performance. The normative mean is 50 with standard deviation of 10.
Outcome measures
| Measure |
Intermediate-Risk Group
n=53 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=27 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
Prior to Maintenance Therapy
|
44.6 score on a scale
Standard Deviation 12.6
|
53.0 score on a scale
Standard Deviation 0.0
|
39.0 score on a scale
Standard Deviation 17.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
48 Months Off Therapy
|
43.6 score on a scale
Standard Deviation 7.3
|
44.3 score on a scale
Standard Deviation 10.1
|
44.2 score on a scale
Standard Deviation 23.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
60 Months Off Therapy
|
40.6 score on a scale
Standard Deviation 9.2
|
34.0 score on a scale
Standard Deviation 15.7
|
39.4 score on a scale
Standard Deviation 16.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
Baseline
|
47.5 score on a scale
Standard Deviation 16.3
|
37.3 score on a scale
Standard Deviation 11.9
|
62.0 score on a scale
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
Completion Of Therapy
|
48.5 score on a scale
Standard Deviation 8.6
|
46.0 score on a scale
|
40.0 score on a scale
Standard Deviation 13.6
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
12 Months Off Therapy
|
43.8 score on a scale
Standard Deviation 11.1
|
39.0 score on a scale
Standard Deviation 9.2
|
43.1 score on a scale
Standard Deviation 18.2
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
24 Months Off Therapy
|
43.6 score on a scale
Standard Deviation 10.3
|
32.0 score on a scale
Standard Deviation 16.0
|
48.2 score on a scale
Standard Deviation 11.5
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Motor Integration (VMI) T-scores
36 Months Off Therapy
|
41.3 score on a scale
Standard Deviation 8.9
|
36.8 score on a scale
Standard Deviation 13.6
|
45.6 score on a scale
Standard Deviation 14.1
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, prior to maintenance therapy, completion of therapy, and 12 months, 24 months, 36 months, 48 months, and 60 months off therapyPopulation: Eligible patients with scores at any of the data collection timepoints were included. Sample sizes differ across timepoints as not all subjects had scores for all timepoints.
Scores measuring visual-spatial reasoning were obtained from Visual Perception T-scores on the Beery Visual Motor Integration (VMI) instrument. Higher scores indicate better performance. The normative mean is 50 with a standard deviation of 10.
Outcome measures
| Measure |
Intermediate-Risk Group
n=53 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=14 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=22 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
Baseline
|
31.6 score on a scale
Standard Deviation 12.2
|
33.7 score on a scale
Standard Deviation 9.5
|
66.0 score on a scale
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
Prior to Maintenance Therapy
|
40.2 score on a scale
Standard Deviation 12.2
|
56.0 score on a scale
Standard Deviation 8.5
|
32.0 score on a scale
Standard Deviation 7.1
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
Completion of Therapy
|
39.8 score on a scale
Standard Deviation 12.3
|
18.5 score on a scale
Standard Deviation 26.2
|
39.0 score on a scale
Standard Deviation 16.4
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
12 Months Off Therapy
|
41.0 score on a scale
Standard Deviation 14.5
|
33.0 score on a scale
|
42.3 score on a scale
Standard Deviation 14.7
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
24 Months Off Therapy
|
40.1 score on a scale
Standard Deviation 13.4
|
32.0 score on a scale
Standard Deviation 8.9
|
43.4 score on a scale
Standard Deviation 15.0
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
36 Months Off Therapy
|
41.0 score on a scale
Standard Deviation 13.6
|
48.8 score on a scale
Standard Deviation 18.7
|
51.2 score on a scale
Standard Deviation 17.8
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
48 Months Off Therapy
|
46.1 score on a scale
Standard Deviation 11.3
|
42.7 score on a scale
Standard Deviation 8.3
|
48.6 score on a scale
Standard Deviation 24.9
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Neurocognitive Performance Related to Visual-spatial Reasoning as Measured by Visual Perception T-scores
60 Months Off Therapy
|
42.3 score on a scale
Standard Deviation 13.3
|
36.0 score on a scale
Standard Deviation 12.7
|
43.1 score on a scale
Standard Deviation 18.8
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0016 Change in FA per month
Interval 0.0015 to 0.0018
|
0.0017 Change in FA per month
Interval 0.0015 to 0.0019
|
0.0019 Change in FA per month
Interval 0.0016 to 0.0022
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0017 change in FA per month
Interval 0.0015 to 0.0018
|
0.0017 change in FA per month
Interval 0.0014 to 0.0019
|
0.0019 change in FA per month
Interval 0.0015 to 0.0022
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0014 Change in FA per month
Interval 0.0012 to 0.0015
|
0.0016 Change in FA per month
Interval 0.0013 to 0.0018
|
0.0015 Change in FA per month
Interval 0.0012 to 0.0019
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left parietal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0014 Change in FA per month
Interval 0.0012 to 0.0016
|
0.0016 Change in FA per month
Interval 0.0013 to 0.0018
|
0.0016 Change in FA per month
Interval 0.0012 to 0.002
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0015 Change in FA per month
Interval 0.0014 to 0.0017
|
0.0013 Change in FA per month
Interval 0.0011 to 0.0016
|
0.0016 Change in FA per month
Interval 0.0013 to 0.0019
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left occipital lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0020 Change in FA per month
Interval 0.0018 to 0.0022
|
0.0015 Change in FA per month
Interval 0.0012 to 0.0018
|
0.0021 Change in FA per month
Interval 0.0017 to 0.0025
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0013 Change in FA per month
Interval 0.0011 to 0.0014
|
0.0013 Change in FA per month
Interval 0.0011 to 0.0015
|
0.0014 Change in FA per month
Interval 0.0012 to 0.0017
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in left temporal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Neurostructure, Especially White Matter Volume and Integrity
|
0.0013 Change in FA per month
Interval 0.0011 to 0.0014
|
0.0014 Change in FA per month
Interval 0.0011 to 0.0016
|
0.0014 Change in FA per month
Interval 0.0011 to 0.0017
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in frontal lobe over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Quantitative Magnetic Resonance (MR) Measures in the Frontal Lobe
|
0.0017 Change in FA per month
Interval 0.0015 to 0.0018
|
0.0017 Change in FA per month
Interval 0.0014 to 0.0019
|
0.0019 Change in FA per month
Interval 0.0016 to 0.0022
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline (month 0) to 60 months (therapy duration lasted approximately 48 weeks or 11 months)Population: Eligible infratentorial medulloblastoma, ependymoma, and pineoblastoma patients(n=75) were included.
Quantitative MRI measures Fractional Anisotropy (FA) change per month in right frontal-parietal region over time in each risk group will be assessed using a random effects model incorporating various covariates. Covariates to be considered include age at diagnosis, time since diagnosis and risk-arm. Differences in quantitative MRI measures of neurostructure volume and integrity between patient groups will be evaluated as a metric of structural neurotoxicity of therapy. Fractional anisotropy (FA) is a scalar unitless measure that quantifies the degree of anisotropy of a diffusion process, particularly in the context of diffusion tensor imaging (DTI) used in MRI scans. FA values range from 0 to 1
Outcome measures
| Measure |
Intermediate-Risk Group
n=43 Participants
Patients with no evidence of metastatic disease (M0) medulloblastoma or nodular desmoplastic histology with less than a gross total resection (GTR), other histologic diagnoses with no metastatic disease
|
High-Risk Group
n=20 Participants
Patients with central nervous system (CNS) metastatic disease
|
Low-Risk Group
n=12 Participants
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic histology, or high grade glioma
|
Low-risk Group 3 Patients
Group 3 (G3) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 3 Patients
Group 3 medulloblastoma subgroup patients in the high-risk group
|
Low-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the low-risk group
|
Intermediate-risk Group 4 Patients
Group 4 (G4) medulloblastoma subgroup patients in the intermediate-risk group
|
High-risk Group 4 Patients
Group 4 medulloblastoma subgroup patients in the high-risk group
|
|---|---|---|---|---|---|---|---|---|---|
|
Change in Quantitative MR Measures in the Right Frontal-parietal Regions
|
0.0015 Change in FA per month
Interval 0.0014 to 0.0017
|
0.0016 Change in FA per month
Interval 0.0014 to 0.0019
|
0.0017 Change in FA per month
Interval 0.0014 to 0.0021
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Low-Risk Group
Serious events: 3 serious events
Other events: 55 other events
Deaths: 10 deaths
Intermediate-Risk Group
Serious events: 7 serious events
Other events: 145 other events
Deaths: 58 deaths
High-Risk Group
Serious events: 5 serious events
Other events: 70 other events
Deaths: 49 deaths
Serious adverse events
| Measure |
Low-Risk Group
n=57 participants at risk
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
|
Intermediate-Risk Group
n=156 participants at risk
Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.
|
High-Risk Group
n=76 participants at risk
Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Platelets
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Cardiac disorders
Hypotension
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
2/156 • Number of events 2 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.9%
3/156 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
General disorders
Weight loss
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam), Oral cavity
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Perforation, GI, Duodenum
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
2/156 • Number of events 2 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Vascular disorders
Hemorrhage/Bleeding - Other
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L), Pharynx
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Upper airway NOS
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection - Other
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Blood
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Catheter-related
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Eye NOS
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Hydrocephalus
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Irritability (children <3 years of age)
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Neurology - Other
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Neuropathy: motor
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Seizure
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Speech impairment (e.g., dysphasia or aphasia)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
2.6%
2/76 • Number of events 2 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Wound
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
Other adverse events
| Measure |
Low-Risk Group
n=57 participants at risk
Patients with gross total resection (GTR)/no evidence of metastatic disease (M0) medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.
|
Intermediate-Risk Group
n=156 participants at risk
Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.
|
High-Risk Group
n=76 participants at risk
Patients with central nervous system (CNS) metastatic disease will receive induction chemotherapy and high-risk therapy.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
63.2%
36/57 • Number of events 83 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
59.0%
92/156 • Number of events 169 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
63.2%
48/76 • Number of events 120 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
56.1%
32/57 • Number of events 60 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
36.5%
57/156 • Number of events 124 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
13.2%
10/76 • Number of events 20 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
42.1%
24/57 • Number of events 38 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
28.8%
45/156 • Number of events 83 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
7.9%
6/76 • Number of events 11 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Vomiting
|
17.5%
10/57 • Number of events 11 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
16.0%
25/156 • Number of events 32 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
28.9%
22/76 • Number of events 29 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
22.8%
13/57 • Number of events 15 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.8%
9/156 • Number of events 20 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.9%
3/76 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Catheter-related
|
19.3%
11/57 • Number of events 14 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
10.9%
17/156 • Number of events 19 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
10.5%
8/76 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Anorexia
|
10.5%
6/57 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
9.6%
15/156 • Number of events 16 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
15.8%
12/76 • Number of events 13 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Catheter-related
|
14.0%
8/57 • Number of events 8 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
12.2%
19/156 • Number of events 26 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
6.6%
5/76 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Platelets
|
12.3%
7/57 • Number of events 19 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 10 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
11.8%
9/76 • Number of events 13 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
10.5%
6/57 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 8 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
2.6%
2/76 • Number of events 2 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Diarrhea
|
10.5%
6/57 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
8.3%
13/156 • Number of events 14 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
10.5%
8/76 • Number of events 11 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (functional/symptomatic), Oral cavity
|
7.0%
4/57 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
4.5%
7/156 • Number of events 8 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
9.2%
7/76 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
5.3%
3/57 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 12 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
9.2%
7/76 • Number of events 10 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Skin (cellulitis)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
4.5%
7/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
9.2%
7/76 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Seizure
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
2.6%
4/156 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
9.2%
7/76 • Number of events 7 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Blood
|
8.8%
5/57 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.2%
5/156 • Number of events 6 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
6.6%
5/76 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
General disorders
Weight loss
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/156 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
7.9%
6/76 • Number of events 6 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Nausea
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.8%
6/156 • Number of events 6 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
7.9%
6/76 • Number of events 6 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam), Oral cavity
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
7.1%
11/156 • Number of events 12 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection - Other
|
7.0%
4/57 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 11 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Nervous system disorders
Hydrocephalus
|
3.5%
2/57 • Number of events 2 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
6.6%
5/76 • Number of events 5 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Blood
|
3.5%
2/57 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.8%
9/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Ear and labyrinth disorders
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program
|
5.3%
3/57 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.64%
1/156 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
1/76 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Gastrointestinal disorders
Dehydration
|
5.3%
3/57 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.9%
3/76 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Upper airway NOS
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
2.6%
4/156 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Infections and infestations
Infection, Urinary tract NOS
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
1.3%
2/156 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.3%
4/76 • Number of events 4 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
3.5%
2/57 • Number of events 6 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 8 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
0.00%
0/76 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
0.00%
0/57 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 8 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.9%
3/76 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
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Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
1.8%
1/57 • Number of events 1 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
5.1%
8/156 • Number of events 9 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
|
3.9%
3/76 • Number of events 3 • All adverse events grades 3, 4, and 5 which occur during treatment and for 30 days after the end of treatment, and events which occur later than 30 days after the end of treatment which are felt to be at least possibly related to treatment, to the time of off study, were collected with some exceptions noted in the additional description section, up to 6 years..
Per protocol, some grade 3 and 4 hematologic toxicities, grade 3 elevation in serum ALT or AST, grade 3 and 4 electrolyte abnormalities, and total parenteral nutrition or intravenous fluids administered to prevent significant weight loss/malnutrition were not collected, especially if they occurred from the beginning of induction chemotherapy. The one patient in the high-risk group who did not start therapy due to early disease progression was excluded from adverse event results.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MSA states Site is unable to publish until all completed case report forms have been delivered to Sponsor, (Study Completion). Site shall have the right to publish after publication of a multi-center publication coordinated by the Sponsor or (12) mths. after Study Completion; provided, that prior to any such publication or public release of such data, Site shall furnish Sponsor with a copy of any proposed publication at least (45)days in advance of the proposed publication or presentation date.
- Publication restrictions are in place
Restriction type: OTHER