Trial Outcomes & Findings for Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma (NCT NCT00336024)

Last Updated: 2026-01-23

Results Overview

At the end of consolidation, the number of evaluable patients treated with intensive chemotherapy with methotrexate who achieved CR or not will be compared to those who achieved CR or not after treated with the same intensive chemotherapy without methotrexate. The CR rates between these two groups will be compared at a significance level of 0.1 using one-sided Chi-square test. Complete Response (CR) requires: CR for target lesions: disappearance of all target lesions, CR for non-target lesions: disappearance of all non-target lesions and no new lesions. No CR is any response not fitting the definition of CR.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

At the end of consolidation treatment

Results posted on

2026-01-23

Participant Flow

Children less than 36 months with high risk medulloblastoma/PNET were enrolled in the study. The first eligible patient was enrolled on October 22, 2007 and the last patient was enrolled on April 23, 2014.

This is a Phase 3 randomized trial designed to determine whether or not the addition of high dose Methotrexate will achieve a higher complete response rate.

Participant milestones

Participant milestones
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	46	45
Overall Study COMPLETED	26	26
Overall Study NOT COMPLETED	20	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Death	2	1
Overall Study Physician Decision	4	1
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	1	2
Overall Study Failure to fulfill consolidation	1	1
Overall Study Progressive Disease	4	7
Overall Study Ineligible	7	7

Baseline Characteristics

Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Total n=77 Participants Total of all reporting groups
Age, Continuous	1.97 years STANDARD_DEVIATION 0.75 • n=270 Participants	1.73 years STANDARD_DEVIATION 0.87 • n=4 Participants	1.85 years STANDARD_DEVIATION 0.82 • n=9 Participants
Sex: Female, Male Female	20 Participants n=270 Participants	18 Participants n=4 Participants	38 Participants n=9 Participants
Sex: Female, Male Male	19 Participants n=270 Participants	20 Participants n=4 Participants	39 Participants n=9 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=270 Participants	11 Participants n=4 Participants	15 Participants n=9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=270 Participants	26 Participants n=4 Participants	59 Participants n=9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=270 Participants	1 Participants n=4 Participants	3 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Asian	1 Participants n=270 Participants	1 Participants n=4 Participants	2 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	2 Participants n=270 Participants	2 Participants n=4 Participants	4 Participants n=9 Participants
Race (NIH/OMB) White	30 Participants n=270 Participants	30 Participants n=4 Participants	60 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=270 Participants	0 Participants n=4 Participants	0 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=270 Participants	5 Participants n=4 Participants	11 Participants n=9 Participants

PRIMARY outcome

Timeframe: At the end of consolidation treatment

Population: Per protocol, only evaluable patients are included.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=29 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=30 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate Complete response	13 Participants	15 Participants
Number of Patients Who Have Either a Complete Response (CR) Rate or No Complete Response Rate No Complete response	16 Participants	15 Participants

SECONDARY outcome

Timeframe: At baseline

Population: 13 patients without molecular data, because of lack of sufficient materials or poor quality of the data, were not included in this analysis.

The number of patients will be reported for this analysis by Molecular Sub-types of MB, CNS-PNETs/EBTs

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=34 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=30 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Medulloblastoma, group 4 subgroup	0 Participants	2 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Medulloblastoma, sonic hedgehog subgroup	5 Participants	6 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Medulloblastoma, group 3 subgroup	15 Participants	10 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Embryonal tumor with multilayered rosettes	9 Participants	5 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Pineoblastoma	3 Participants	6 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Atypical teratoid/rhabdoid tumor	1 Participants	0 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort High-grade glioma	1 Participants	0 Participants
Number of Participants With Molecular Sub-types of MB, CNS-PNETs/EBTs Represented in the ACNS0334 Cohort Pleomorphic xanthoastrocytoma	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to up to 5 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

EFS was defined as time from enrollment to the occurrence of first event (disease progression/relapse, secondary malignancy, death from any cause) or date of last contact for patients who are event-free. The percentage of participants with EFS and 80% confidence interval were provided. The difference in incidence for the two treatment regimens were compared using a one-sided log-rank test with a significance level of 0.1.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Percentage of Participants With Event Free Survival (EFS)	43.6 percentage of participants with EFS Interval 33.3 to 53.4	52.6 percentage of participants with EFS Interval 41.8 to 62.4

SECONDARY outcome

Timeframe: Baseline to up to 5 years

Population: All Eligible Participants who relapsed/disease progressed in the study.

The patterns of failure for relapse/disease progression will be provided for patients treated with/without methotrexate drug in three categories, namely local, distant, and both local and distant. The number of patients with each type of failure will be listed per arm. The two groups will be compared to determine if the pattern of failure distribution is different between the two arms using Fisher exact test.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=20 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=16 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patterns of Failure Local	7 Participants	6 Participants
Patterns of Failure Distant	8 Participants	7 Participants
Patterns of Failure Both Local and Distant	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Beginning of treatment to the end of consolidation

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Event is defined as the first occurrence of any acute toxicity. Estimates will be obtained using life-table methods. Patients who have progression or recurrence of disease will be censored in this analysis. Difference in incidence for the two treatment regimens will be compared using log-rank test.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Percentage of Participants With Any Acute Adverse Events	97.4 percentage of participants Interval 88.5 to 99.8	97.2 percentage of participants Interval 87.7 to 99.8

SECONDARY outcome

Timeframe: Beginning of treatment to the end of consolidation

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Per protocol, hearing was assessed pretreatment and at regular specified intervals during treatment and off therapy, using DPOAE, audiogram or Brainstem Evoked Auditory. Per CTCAE V4.0 grade 3 Hearing impaired is defined as follows; Pediatric (on a 1,2,3,4, 6 and 8 kHz audiogram): hearing loss sufficient to indicate therapeutic intervention, including hearing aids, threshold shift \>20 dB at 3 kHz and above in at least one ear, additional speech-language related services as indicated. Per CTCAE V4.0 grade 4 Hearing impaired is defined as follows; Pediatric Audiologic indication for cochlear implant and additional speech-language related services as indicated.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Acute Hearing Loss and No Acute Hearing Loss No Acute Hearing Loss	32 Participants	32 Participants
Number of Participants With Acute Hearing Loss and No Acute Hearing Loss Acute Hearing Loss	7 Participants	6 Participants

SECONDARY outcome

Timeframe: Off-treatment up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. "Normal" and "Abnormal" are defined at each institution by the laboratory standards where the blood tests are run. Primary Hypothyroidism/Subclinical Compensatory Hypothyroidism is defined as patients with Free T4 level less than "Institutional" Normal or equal to "Institutional" Normal with TSH level greater than "Institutional" Normal.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism	3 Participants	5 Participants

SECONDARY outcome

Timeframe: Off-treatment up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. "Normal" and "Abnormal" are defined at each institution by the laboratory standards where the blood tests are run. Central Hypothyroidism is defined as Free T4 level less than "Institutional" Normal with TSH less than or equal to "Institutional" Normal.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Chronic Central Hypothyroidism	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Off-treatment up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Low Somatomedin C is defined as patients with somatomedin C value less than institutional normal. As numbers are too small, descriptive statistics such as number will be reported for this analysis. Growth hormone function was assessed as per ACNS0334 Endocrine Guidelines. Low Somatomedin C levels are defined at each institution by the laboratory standards where the blood tests are run.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Chronic Low Somatomedin C	2 Participants	5 Participants

SECONDARY outcome

Timeframe: Beginning of off-treatment to up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

The number of patients who had "Diabetes Insipidus" and on DDAVP will be reported for this analysis due to small numbers..

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Chronic Diabetes Insipidus	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Off-treatment up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

The number of patients who had secondary malignancy will be reported for this analysis due to small numbers.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Secondary Malignancies	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Off-treatment up to 9 years

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

The number of patients who are reported to have abnormal hearing, graded according to CTCAE 4.0 or not, with onset while on therapy or when off therapy which persisted after off therapy will be reported and will be compared using Fisher exact test.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Number of Participants With Chronic/Late Hearing Loss and No Chronic/Late Hearing Loss Chronic/Late Hearing Loss	12 Participants	13 Participants
Number of Participants With Chronic/Late Hearing Loss and No Chronic/Late Hearing Loss No Chronic/Late Hearing Loss	27 Participants	25 Participants

SECONDARY outcome

Timeframe: Beginning of treatment to the end of consolidation

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Rates of gastrointestinal toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with gastrointestinal toxicities between the two treatment regimens will be compared using a Chi-square test.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Rates of Gastrointestinal Toxicities GI Tox Consolidation Cycle I	11 Participants	14 Participants
Rates of Gastrointestinal Toxicities No GI Tox Consolidation Phase II	32 Participants	28 Participants
Rates of Gastrointestinal Toxicities GI Tox Consolidation Cycle III	5 Participants	6 Participants
Rates of Gastrointestinal Toxicities No GI Tox Consolidation Cycle III	34 Participants	32 Participants
Rates of Gastrointestinal Toxicities No GI Tox Induction Cycle II	35 Participants	28 Participants
Rates of Gastrointestinal Toxicities GI Tox Induction Cycle I	8 Participants	12 Participants
Rates of Gastrointestinal Toxicities No GI Tox Induction Cycle I	31 Participants	26 Participants
Rates of Gastrointestinal Toxicities GI Tox Induction Cycle II	4 Participants	10 Participants
Rates of Gastrointestinal Toxicities GI Tox Induction Cycle III	4 Participants	8 Participants
Rates of Gastrointestinal Toxicities No GI Tox Induction Cycle III	35 Participants	30 Participants
Rates of Gastrointestinal Toxicities No GI Tox Consolidation Cycle I	28 Participants	24 Participants
Rates of Gastrointestinal Toxicities GI Tox Consolidation Cycle II	7 Participants	10 Participants

SECONDARY outcome

Timeframe: Beginning of treatment to the end of consolidation

Population: Per protocol all eligible patients randomized to treatment should be included in the analysis.

Rates of nutritional toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with nutritional toxicities between the two treatment regimens will be compared using a Chi-square test.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Rates of Nutritional Toxicities Nutritional Disorders Induction Cycle II	13 Participants	13 Participants
Rates of Nutritional Toxicities Nutritional Disorders Induction Cycle I	10 Participants	17 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Induction Cycle I	29 Participants	21 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Induction Cycle II	26 Participants	25 Participants
Rates of Nutritional Toxicities Nutritional Disorders Induction Cycle III	7 Participants	12 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Induction Cycle III	32 Participants	26 Participants
Rates of Nutritional Toxicities Nutritional Disorders Consolidation Cycle I	12 Participants	8 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Consolidation Cycle I	27 Participants	30 Participants
Rates of Nutritional Toxicities Nutritional Disorders Consolidation Cycle II	9 Participants	5 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Consolidation Cycle II	30 Participants	33 Participants
Rates of Nutritional Toxicities Nutritional Disorders Consolidation Cycle III	10 Participants	5 Participants
Rates of Nutritional Toxicities No Nutritional Disorders Consolidation Cycle III	29 Participants	33 Participants

SECONDARY outcome

Timeframe: 60 months (+/- 3 months)

Population: Of the 77 eligible participants in ACNS0334, only 4 patients completed assessments in ALTE07C1 study. The targeted number of participants to achieve target power and statistically reliable results was not achieved and therefore the data is statistically uninterpretable.

Three tools are used to assess intelligence (IQ) depending on age. The range of IQ scores is 40-160 (mean=100, SD=15); range for the Processing Speed Index (PSI)=45-155. Higher scores represent better functioning. (1) Wechsler Preschool and Primary Scale of Intelligence-4th Edition (WPPSI-IV) is used for ages 2.5 to 6 years. Bug Search and Cancellation subtests are summed to calculate PSI. (2) Wechsler Intelligence Scales for Children-5th Edition (WISC-V) is used for ages 6 - 16 years. Symbol Search and Coding subtests are summed to calculate PSI. (3) Wechsler Adult Intelligence Scales-4th Edition (WAIS-IV) is used for ages 16 and older. Symbol Search and Coding subtests are summed to calculate PSI. The Pediatric Quality of Life Inventory Version 4 (PedsQL) measures health-related quality of life (QOL). Parents complete the measure for children ages 2-17, and patients \> 18 complete a self-report version. Total scores range from 0-100, with higher scores representing better QOL.

Outcome measures

Outcome measures
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=2 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=2 Participants Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI). Total Quality of Life Score	60.5 scores on a scale Interval 54.0 to 67.0	56.5 scores on a scale Interval 35.0 to 78.0
Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI). Intelligence Quotient	77.0 scores on a scale Interval 71.0 to 83.0	78.5 scores on a scale Interval 74.0 to 83.0
Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI). Processing Speed Index	82.0 scores on a scale Interval 78.0 to 86.0	89.0 scores on a scale Interval 89.0 to 89.0

Adverse Events

Arm I (Patients Treated Without Methotrexate (MTX))

Serious events: 8 serious events

Other events: 39 other events

Deaths: 18 deaths

Arm II (Patients Treated With MTX)

Serious events: 3 serious events

Other events: 36 other events

Deaths: 15 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Patients Treated Without Methotrexate (MTX)) n=39 participants at risk Patients receive vincristine sulfate IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Arm II (Patients Treated With MTX) n=38 participants at risk Patients receive vincristine sulfate IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and filgrastim (G-CSF) IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Colitis	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Gastrointestinal disorders Jejunal obstruction	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Gastrointestinal disorders Jejunal perforation	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
General disorders Death NOS, Related to progressive disease and not due to protocol therapy	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Hepatobiliary disorders Portal hypertension	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Infections and infestations Sepsis	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Metabolism and nutrition disorders Hyponatremia	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) osteosarcoma in field of radiation administered for first recurrence, p53 predisposition syndrome	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Nervous system disorders Seizure	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.1% 2/39 • Number of events 2 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	2.6% 1/38 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.
Vascular disorders Capillary leak syndrome	2.6% 1/39 • Number of events 1 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.	— 0/0 Adverse Events/Serious Adverse Events were reported for all eligible patients (n=77) by treatment arm in the study. The total number of participants at risk represents total number of eligible patients in the study by treatment arm.

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 352-273-0558

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
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