NCT00653068 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2024-04-23

This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Event-free Survival

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Toxic Death

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outcome · POSTED

Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT) * Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible * Patients with MRI evidence of spinal disease are eligible * Must have undergone definitive surgery in the past 31 days * Cranial MRI (with and without gadolinium) must be done pre-operatively * Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28 days after surgery * Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium) * Life expectancy \> 8 weeks * ANC \> 1,000/uL * Platelet count \> 100,000/uL (transfusion independent) * Hemoglobin \> 8 g/dL (RBC transfusions allowed) * Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR \>= 60 mL/min * Total bilirubin =\< 1.5 times upper limit of normal (ULN) for age * AST and ALT \< 2 times ULN for age * Shortening fraction of \>= 27% by echocardiogram OR ejection fraction of \>= 47% by radionuclide angiogram * No evidence of dyspnea at rest * Pulse oximetry \> 94% on room air * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior radiotherapy or chemotherapy except for the following: * Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged) * Prior corticosteroids allowed
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Within 2-6 weeks after induction therapy or radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. After consolidation therapy, patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks.
intervention Names
Radiation: 3-Dimensional Conformal Radiation Therapy
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Drug: Carboplatin
Drug: Cisplatin
Drug: Cyclophosphamide
Drug: Etoposide
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Thiotepa
Drug: Vincristine Sulfate
label
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
type
EXPERIMENTAL
description
Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV on day 1; leucovorin calcium orally or IV; etoposide IV on days 4, 5, and 6; cyclophosphamide IV on days 4 and 5; cisplatin IV on day 6, and G-CSF IV or SC on day 7 until ANC recovers. Patients undergo 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks. Within 2-6 weeks after completion of radiation therapy, patients receive high-dose carboplatin IV and high-dose thiotepa IV on days 1 and 2 and undergo autologous PBSC rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily until ANC recovers. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
intervention Names
Radiation: 3-Dimensional Conformal Radiation Therapy
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Drug: Carboplatin
Drug: Cisplatin
Drug: Cyclophosphamide
Drug: Etoposide
Biological: Filgrastim
Other: Laboratory Biomarker Analysis
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Thiotepa
Drug: Vincristine Sulfate
label
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
type
EXPERIMENTAL

interventions

arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Undergo 3D-CRT
name
3-Dimensional Conformal Radiation Therapy
other Names
3-dimensional radiation therapy
3D Conformal
3D CONFORMAL RADIATION THERAPY
3D CRT
3D radiotherapy
3D-CRT
Conformal Therapy
Radiation Conformal Therapy
Radiation, 3D Conformal
Three dimensional external beam radiation therapy (procedure)
type
RADIATION
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Undergo autologous PBSC rescue
name
Autologous Hematopoietic Stem Cell Transplantation
other Names
AHSCT
Autologous
Autologous Hematopoietic Cell Transplantation
Autologous Stem Cell Transplant
Autologous Stem Cell Transplantation
Stem Cell Transplantation, Autologous
type
PROCEDURE
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Carboplatin
other Names
Blastocarb
Carboplat
Carboplatin Hexal
Carboplatino
Carboplatinum
Carbosin
Carbosol
Carbotec
CBDCA
Displata
Ercar
JM-8
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Cisplatin
other Names
Abiplatin
Blastolem
Briplatin
CDDP
Cis-diammine-dichloroplatinum
Cis-diamminedichloridoplatinum
Cis-diamminedichloro Platinum (II)
Cis-diamminedichloroplatinum
Cis-dichloroammine Platinum (II)
Cis-platinous Diamine Dichloride
Cis-platinum
Cis-platinum II
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Cyclophosphamide
other Names
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B-518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
CP monohydrate
CTX
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Etoposide
other Names
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP 16213
VP-16
VP-16-213
VP16
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV or SC
name
Filgrastim
other Names
Filgrastim Biosimilar Filgrastim-sndz
Filgrastim Biosimilar Tbo-filgrastim
Filgrastim XM02
Filgrastim-aafi
Filgrastim-ayow
Filgrastim-sndz
G-CSF
Granix
Neupogen
Neutroval
Nivestym
r-metHuG-CSF
type
BIOLOGICAL
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV or PO
name
Leucovorin Calcium
other Names
Adinepar
Calcifolin
Calcium (6S)-Folinate
Calcium Folinate
Calcium Leucovorin
Calfolex
Calinat
Cehafolin
Citofolin
Citrec
Citrovorum Factor
Cromatonbic Folinico
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Methotrexate
other Names
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Thiotepa
other Names
1,1',1''-Phosphinothioylidynetrisaziridine
Girostan
N,N', N''-Triethylenethiophosphoramide
Oncotiotepa
STEPA
Tepadina
TESPA
Tespamin
Tespamine
Thio-Tepa
Thiofosfamide
Thiofozil
type
DRUG
arm Group Labels
Arm I (chemotherapy, autologous PBSC, 3D-CRT)
Arm II (chemotherapy, 3D-CRT, autologous PBSC)
description
Given IV
name
Vincristine Sulfate
other Names
Kyocristine
Leurocristine Sulfate
Leurocristine, sulfate
Oncovin
Vincasar
Vincosid
Vincrex
Vincristine, sulfate
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 70
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
measure
Event-free Survival
time Frame
Up to 4 years after study enrollment
description
Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored.
measure
Overall Survival (OS)
time Frame
Up to 4 years after study enrollment
description
The number of patients who experience death that is considered to be primarily attributable to complications of treatment.
measure
Toxic Death
time Frame
During and after completion of study treatment up to 1 year after enrollment.

secondary Outcomes

description
Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.
measure
Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy
time Frame
During protocol therapy up to 1 year after enrollment.

Full study description

brief Summary: This phase III trial studies the side effects of combination chemotherapy, 3-dimensional conformal radiation therapy, and an autologous peripheral blood stem cell transplant, and to see how well they work in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.
detailed Description: PRIMARY OBJECTIVES: I. To determine the 6-, 12-, and 24-month event-free survival and overall survival of children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT), diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell rescue, and radiation therapy. II. To compare the outcome of very young patients (under 3 years old) on this study whose histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and CCG-9921. SECONDARY OBJECTIVES: I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy. II. To contribute tumor samples from which biologic and gene expression data can be developed to yield prognostic indicators and provide direction for future treatment strategies. III. To develop a clinical and biologic database on which future studies can be based. OUTLINE: INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally (PO) or IV every 6 hours until the serum methotrexate level is \< 0.1 micromoles. 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\*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is \> 1,000/uL post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 6 x 10\^6 CD34+ cells/kg have been collected. Treatment repeats every 21 days for 2 courses. After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease are assigned to 1 of 2 arm. ARM I ((patients less than 6 months, infratentorial site with M0 involvement or patients less than 12 months, supratentorial site with M0 involvement or patients with disseminated disease of any primary site or age): CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. RADIATION THERAPY: Patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks. ARM II (patients greater than or equal to 6 months, infratentorial site with M0 involvement or patients greater than or equal to 12 months, supratentorial site with M0 involvement): Patients undergo 3D-CRT as in Arm I. Within 2-6 weeks after completion of radiation therapy, patients receive consolidation therapy and stem cell rescue as in Arm I NOTE: \*The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of \< 0.1 micromoles. After completion of study treatment, patients are followed periodically for up to 10 years.

Source references

references

citation
Mazzarella J, Heathcock JC. A Randomized Feasibility Study of Rehabilitation Targeting Upper Extremity Function and Participation Using Hippotherapy and the Equine Environment for Children with Cerebral Palsy and Autism Spectrum Disorder. J Integr Complement Med. 2025 Feb;31(2):196-208. doi: 10.1089/jicm.2024.0292. Epub 2024 Nov 8.
pmid
39515374
type
DERIVED
citation
Reddy AT, Krailo MD, Buxton AB, Strother DR, Huang A, Zhou T, Judkins AR, Burger PC, Pollack IF, Williams-Hughes C, Fouladi M, Ho B, Mazewski CM, Lewis VA, Vezina LG, Booth TN, Mahajan A. Reply to S.A. Upadhyaya. J Clin Oncol. 2020 Oct 1;38(28):3353-3354. doi: 10.1200/JCO.20.01573. Epub 2020 Jul 30. No abstract available.
pmid
32730180
type
DERIVED