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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00653068
Recruitment Status : Active, not recruiting
First Posted : April 4, 2008
Results First Posted : February 13, 2017
Last Update Posted : February 28, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Childhood Atypical Teratoid/Rhabdoid Tumor
Interventions 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
Enrollment 70
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment
Hide Arm/Group Description

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.

Consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses (C) and 3D-CRT to the brain (and the spine if needed) 5 days a week for 5-6 weeks (R), the order of which depends on patient age, in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 70
Completed 20
Not Completed 50
Reason Not Completed
Death             9
Lack of Efficacy             34
Physician Decision             4
Withdrawal by Subject             1
Ineligible             2
Arm/Group Title Stratum I Stratum II Stratum III Stratum IV Total
Hide Arm/Group Description Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT. Infants with INI1 mutation only based diagnosis (histology is not consistent with AT/RT). Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT. Older children with INI1 mutation only based diagnosis. Total of all reporting groups
Overall Number of Baseline Participants 58 0 12 0 70
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
<=18 years
58
 100.0%
12
 100.0%
70
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
1
(0 to 2)
4
(3 to 14)
1
(0 to 14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
Female
28
  48.3%
8
  66.7%
36
  51.4%
Male
30
  51.7%
4
  33.3%
34
  48.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
Hispanic or Latino
15
  25.9%
5
  41.7%
20
  28.6%
Not Hispanic or Latino
39
  67.2%
7
  58.3%
46
  65.7%
Unknown or Not Reported
4
   6.9%
0
   0.0%
4
   5.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
American Indian or Alaska Native
1
   1.7%
0
   0.0%
1
   1.4%
Asian
1
   1.7%
2
  16.7%
3
   4.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
  12.1%
1
   8.3%
8
  11.4%
White
40
  69.0%
7
  58.3%
47
  67.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
9
  15.5%
2
  16.7%
11
  15.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 58 participants 0 participants 12 participants 0 participants 70 participants
Canada
6
  10.3%
2
  16.7%
8
  11.4%
United States
51
  87.9%
10
  83.3%
61
  87.1%
Australia
1
   1.7%
0
   0.0%
1
   1.4%
1.Primary Outcome
Title Event-free Survival
Hide 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.
Time Frame Up to 4 years after study enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.
Arm/Group Title Stratum I Stratum III
Hide Arm/Group Description:
Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Overall Number of Participants Analyzed 57 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated probability
0.3401
(0.2174 to 0.4666)
0.4500
(0.1267 to 0.7345)
2.Primary Outcome
Title Overall Survival (OS)
Hide 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.
Time Frame Up to 4 years after study enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.
Arm/Group Title Stratum I Stratum III
Hide Arm/Group Description:
Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Overall Number of Participants Analyzed 57 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Estimated Probability
0.3888
(0.2582 to 0.5173)
0.5486
(0.1873 to 0.8064)
3.Primary Outcome
Title Toxic Death
Hide Description The number of patients who experience death that is considered to be primarily attributable to complications of treatment.
Time Frame During and after completion of study treatment up to 1 year after enrollment.
Hide Outcome Measure Data
Hide Analysis Population Description
One patient was ineligible in stratum I and one patient was ineligible in stratum III. There were no patients enrolled in Stratum 2 or 4.
Arm/Group Title Stratum I Stratum III
Hide Arm/Group Description:
Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
Overall Number of Participants Analyzed 57 11
Measure Type: Count of Participants
Unit of Measure: Participants
3
   5.3%
1
   9.1%
4.Secondary Outcome
Title Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy
Hide Description Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy.
Time Frame During protocol therapy up to 1 year after enrollment.
Hide Outcome Measure Data
Hide Analysis Population Description
68 eligible patients were evaluable
Arm/Group Title All Patients
Hide Arm/Group Description:
Experimental
Overall Number of Participants Analyzed 68
Measure Type: Count of Participants
Unit of Measure: Participants
Acidosis
1
   1.5%
Acute kidney injury
1
   1.5%
Apnea
2
   2.9%
Adult respiratory distress syndrome
1
   1.5%
Aspiration
3
   4.4%
Atelectasis
1
   1.5%
Catheter related infection
2
   2.9%
Central nervous system necrosis
1
   1.5%
Dehydration
1
   1.5%
Diarrhea
1
   1.5%
Dissmeminated intravascular coagulation (DIC)
1
   1.5%
Enterocolitis
1
   1.5%
Febrile neutropenia
6
   8.8%
Hearing impairment
1
   1.5%
Hematuria
1
   1.5%
Hydrocephalus
1
   1.5%
Hypernatremia
1
   1.5%
Hypoalbuminemia
1
   1.5%
Hypocalcemia
3
   4.4%
Hypoglycemia
2
   2.9%
Hypokalemia
9
  13.2%
Hyponatremia
2
   2.9%
Hypophosphatemia
2
   2.9%
Hypotension
4
   5.9%
Hypoxia
6
   8.8%
Increased Alanine aminotransferase
5
   7.4%
Increased Aspartate aminotransferase
4
   5.9%
Increased Lipase
1
   1.5%
Intracranial hemorrhage
2
   2.9%
ntraoperative venous injury
1
   1.5%
Laryngospasm
1
   1.5%
Left ventricular systolic dysfunction
1
   1.5%
Lung infection
3
   4.4%
Multi-organ failure
1
   1.5%
Mucositis oral
3
   4.4%
Poisoning and procedural complications
1
   1.5%
Other gastrointestinal disorders
1
   1.5%
Other infection
7
  10.3%
Pneumonitis
2
   2.9%
Productive cough
1
   1.5%
Pulmonary edema
1
   1.5%
Recurrent laryngeal nerve palsy
1
   1.5%
Renal calculi
1
   1.5%
Respiratory failure
3
   4.4%
Seizure
2
   2.9%
Sepsis
6
   8.8%
Sinus tachycardia
2
   2.9%
Stridor
2
   2.9%
Upper respiratory infection
1
   1.5%
Vascular access complication
1
   1.5%
Voice alteration
1
   1.5%
Vomiting
1
   1.5%
Weight loss
1
   1.5%
Time Frame [Not Specified]
Adverse Event Reporting Description There were no patients enrolled in Stratum 2 or 4.
 
Arm/Group Title Stratum I Stratum III
Hide Arm/Group Description Infants (<36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT Older children (greater than 36 months of age) with tumor histology and immunohistochemical analysis diagnostic of AT/RT.
All-Cause Mortality
Stratum I Stratum III
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Stratum I Stratum III
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/57 (12.28%)      0/11 (0.00%)    
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  1/57 (1.75%)  1 0/11 (0.00%)  0
Cardiac disorders     
Left ventricular systolic dysfunction  1/57 (1.75%)  1 0/11 (0.00%)  0
General disorders     
Multi-organ failure  1/57 (1.75%)  1 0/11 (0.00%)  0
Infections and infestations     
Enterocolitis infectious  1/57 (1.75%)  1 0/11 (0.00%)  0
Sepsis  2/57 (3.51%)  2 0/11 (0.00%)  0
Upper respiratory infection  1/57 (1.75%)  1 0/11 (0.00%)  0
Investigations     
Lymphocyte count decreased  1/57 (1.75%)  1 0/11 (0.00%)  0
Neutrophil count decreased  1/57 (1.75%)  1 0/11 (0.00%)  0
White blood cell decreased  1/57 (1.75%)  1 0/11 (0.00%)  0
Metabolism and nutrition disorders     
Acidosis  1/57 (1.75%)  1 0/11 (0.00%)  0
Hypoalbuminemia  1/57 (1.75%)  1 0/11 (0.00%)  0
Hypokalemia  2/57 (3.51%)  2 0/11 (0.00%)  0
Hypophosphatemia  1/57 (1.75%)  1 0/11 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1/57 (1.75%)  1 0/11 (0.00%)  0
Nervous system disorders     
Central nervous system necrosis  1/57 (1.75%)  1 0/11 (0.00%)  0
Intracranial hemorrhage  2/57 (3.51%)  2 0/11 (0.00%)  0
Seizure  1/57 (1.75%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Hypoxia  1/57 (1.75%)  1 0/11 (0.00%)  0
Pulmonary edema  1/57 (1.75%)  1 0/11 (0.00%)  0
Respiratory failure  2/57 (3.51%)  2 0/11 (0.00%)  0
Vascular disorders     
Hypotension  1/57 (1.75%)  1 0/11 (0.00%)  0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Stratum I Stratum III
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   43/57 (75.44%)      8/11 (72.73%)    
Blood and lymphatic system disorders     
Anemia  6/57 (10.53%)  6 0/11 (0.00%)  0
Febrile neutropenia  6/57 (10.53%)  6 0/11 (0.00%)  0
Cardiac disorders     
Sinus tachycardia  2/57 (3.51%)  2 0/11 (0.00%)  0
Ear and labyrinth disorders     
Hearing impaired  1/57 (1.75%)  1 0/11 (0.00%)  0
Gastrointestinal disorders     
Diarrhea  1/57 (1.75%)  1 0/11 (0.00%)  0
Gastrointestinal disorders - Other, specify  1/57 (1.75%)  1 0/11 (0.00%)  0
Mucositis oral  2/57 (3.51%)  2 1/11 (9.09%)  1
Vomiting  1/57 (1.75%)  1 0/11 (0.00%)  0
General disorders     
Death NOS  1/57 (1.75%)  1 0/11 (0.00%)  0
Infections and infestations     
Catheter related infection  1/57 (1.75%)  1 1/11 (9.09%)  1
Infections and infestations - Other, specify  7/57 (12.28%)  7 0/11 (0.00%)  0
Lung infection  2/57 (3.51%)  2 1/11 (9.09%)  1
Sepsis  4/57 (7.02%)  4 0/11 (0.00%)  0
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications - Other, specify  1/57 (1.75%)  1 0/11 (0.00%)  0
Intraoperative venous injury  1/57 (1.75%)  1 0/11 (0.00%)  0
Vascular access complication  1/57 (1.75%)  1 0/11 (0.00%)  0
Investigations     
Alanine aminotransferase increased  5/57 (8.77%)  5 0/11 (0.00%)  0
Aspartate aminotransferase increased  4/57 (7.02%)  4 0/11 (0.00%)  0
Investigations - Other, specify  0/57 (0.00%)  0 1/11 (9.09%)  1
Lipase increased  1/57 (1.75%)  1 0/11 (0.00%)  0
Lymphocyte count decreased  18/57 (31.58%)  18 1/11 (9.09%)  1
Neutrophil count decreased  37/57 (64.91%)  37 5/11 (45.45%)  5
Platelet count decreased  31/57 (54.39%)  31 5/11 (45.45%)  5
Weight loss  1/57 (1.75%)  1 0/11 (0.00%)  0
White blood cell decreased  30/57 (52.63%)  30 3/11 (27.27%)  3
Metabolism and nutrition disorders     
Dehydration  0/57 (0.00%)  0 1/11 (9.09%)  1
Hypernatremia  1/57 (1.75%)  1 0/11 (0.00%)  0
Hypocalcemia  2/57 (3.51%)  2 1/11 (9.09%)  1
Hypoglycemia  1/57 (1.75%)  1 1/11 (9.09%)  1
Hypokalemia  6/57 (10.53%)  6 1/11 (9.09%)  1
Hyponatremia  1/57 (1.75%)  1 1/11 (9.09%)  1
Hypophosphatemia  1/57 (1.75%)  1 0/11 (0.00%)  0
Nervous system disorders     
Hydrocephalus  1/57 (1.75%)  1 0/11 (0.00%)  0
Recurrent laryngeal nerve palsy  1/57 (1.75%)  1 0/11 (0.00%)  0
Seizure  0/57 (0.00%)  0 1/11 (9.09%)  1
Renal and urinary disorders     
Acute kidney injury  1/57 (1.75%)  1 0/11 (0.00%)  0
Hematuria  1/57 (1.75%)  1 0/11 (0.00%)  0
Renal calculi  1/57 (1.75%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1/57 (1.75%)  1 0/11 (0.00%)  0
Apnea  2/57 (3.51%)  2 0/11 (0.00%)  0
Aspiration  3/57 (5.26%)  3 0/11 (0.00%)  0
Atelectasis  1/57 (1.75%)  1 0/11 (0.00%)  0
Hypoxia  4/57 (7.02%)  4 1/11 (9.09%)  1
Laryngospasm  1/57 (1.75%)  1 0/11 (0.00%)  0
Pneumonitis  1/57 (1.75%)  1 1/11 (9.09%)  1
Productive cough  1/57 (1.75%)  1 0/11 (0.00%)  0
Respiratory failure  1/57 (1.75%)  1 0/11 (0.00%)  0
Stridor  2/57 (3.51%)  2 0/11 (0.00%)  0
Voice alteration  1/57 (1.75%)  1 0/11 (0.00%)  0
Vascular disorders     
Hypotension  2/57 (3.51%)  2 1/11 (9.09%)  1
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Must obtain prior Sponsor approval.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00653068    
Other Study ID Numbers: ACNS0333
NCI-2009-00337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACNS0333
09-0058
CDR0000592812
COG-ACNS0333
ACNS0333 ( Other Identifier: Childrens Oncology Group )
ACNS0333 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: April 3, 2008
First Posted: April 4, 2008
Results First Submitted: December 20, 2016
Results First Posted: February 13, 2017
Last Update Posted: February 28, 2023