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Cyclophosphamide and Prednisone With or Without Immunoglobulin in Treating Abnormal Muscle Movement in Children With Neuroblastoma

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ClinicalTrials.gov Identifier: NCT00033293
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : October 3, 2016
Last Update Posted : May 22, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Disseminated Neuroblastoma
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Regional Neuroblastoma
Stage 4S Neuroblastoma
Interventions: Biological: therapeutic immune globulin
Other: clinical observation
Drug: cyclophosphamide
Drug: prednisone
Procedure: magnetic resonance imaging
Other: laboratory biomarker analysis
Drug: Corticotropin-Releasing Hormone

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm I (Chemotherapy, Immunoglobulin Therapy)

Patients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hr on day 0. Treatment repeats every 4 wks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 mths and then every other day for 7-15 mths.

Patients receive therapeutic immune globulin IV on days -2 and -1, at wks 4, 8, 12, 16, 20, and 24, and then at mths 8, 10, and 12 after therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with no response after 6 months go off treatment. In case of progression of opsoclonus-myoclonus-ataxia (OMA) during evaluation, patient will be switched to another steroid, corticotropin-releasing hormone (ACTH).
Arm II (Chemotherapy, Observation)

Patients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning on day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 months and then every other day for 7-15 months.

Patients do not receive therapeutic immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.

Participant Flow:   Overall Study
    Arm I (Chemotherapy, Immunoglobulin Therapy)   Arm II (Chemotherapy, Observation)
STARTED   26   27 
COMPLETED   16   9 
NOT COMPLETED   10   18 
Death                0                1 
Lack of Efficacy                5                8 
Lost to Follow-up                0                1 
Physician Decision                3                1 
Withdrawal by Subject                1                0 
Could not be weaned from steroid therapy                1                1 
Treatment refused                0                6 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm I (Chemotherapy, Immunoglobulin Therapy)

Patients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hr on day 0. Treatment repeats every 4 wks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 mths and then every other day for 7-15 mths.

Patients receive therapeutic immune globulin IV on days -2 and -1, at wks 4, 8, 12, 16, 20, and 24, and then at mths 8, 10, and 12 after therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with no response after 6 months go off treatment. In case of progression of opsoclonus-myoclonus-ataxia (OMA) during evaluation, patient will be switched to another steroid, corticotropin-releasing hormone (ACTH).
Arm II (Chemotherapy, Observation)

Patients with intermediate-risk or high-risk neuroblastoma receive chemotherapy (including cyclophosphamide) according to the standard of care for the stage of primary neuroblastoma, beginning on day 0. Patients with low-risk neuroblastoma (and not receiving other chemotherapy) receive cyclophosphamide IV over 1 hour on day 0. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. All patients receive oral prednisone twice daily for 3 months and then every other day for 7-15 months.

Patients do not receive therapeutic immune globulin. Patients with unresponsive opsoclonus-myoclonus-ataxia syndrome after 2 months or progression after 6 months may cross over to arm I.
Total Total of all reporting groups

Baseline Measures
   Arm I (Chemotherapy, Immunoglobulin Therapy)   Arm II (Chemotherapy, Observation)   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 26   27   53 
Age 
[Units: Participants]
Count of Participants 		     
<=18 years      26 100.0%      27 100.0%      53 100.0% 
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 
[Units: Years]
Mean (Standard Deviation) 		 1.4  (0.9)   1.2  (0.5)   1.3  (0.7) 
Sex: Female, Male 
[Units: Participants]
Count of Participants 		     
Female      18  69.2%      15  55.6%      33  62.3% 
Male      8  30.8%      12  44.4%      20  37.7% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants 		     
Hispanic or Latino      5  19.2%      7  25.9%      12  22.6% 
Not Hispanic or Latino      20  76.9%      20  74.1%      40  75.5% 
Unknown or Not Reported      1   3.8%      0   0.0%      1   1.9% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants 		     
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Asian      1   3.8%      0   0.0%      1   1.9% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      5  19.2%      6  22.2%      11  20.8% 
White      19  73.1%      17  63.0%      36  67.9% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      1   3.8%      4  14.8%      5   9.4% 
Region of Enrollment 
[Units: Participants]
 		     
United States   26   27   53 


  Outcome Measures

1.  Primary:   Number of Responders   [ Time Frame: Changes from baseline to 2 months, 6 months, and 1 year ]
  Show Outcome Measure 1

2.  Secondary:   Motor Coordination as Assessed by Neurological Examination and Vineland Adaptive Behavior Scale (VABS)   [ Time Frame: Changes from baseline to the better of 6 months or 1 year ]
  Show Outcome Measure 2

3.  Secondary:   Functional Outcome as Assessed by Age-appropriate Neuropsychological Testing   [ Time Frame: Changes from baseline to the better of 6 months or 1 year ]
  Show Outcome Measure 3

4.  Secondary:   Biology of Neuroblastoma Associated Opsoclonus-myoclonus-ataxia (OMA) Syndrome Specifically by MRI Findings, Anti-neuronal Antibodies, Cerebrospinal Fluid (CSF) Findings and Tumor Biology   [ Time Frame: At diagnosis, 6 months, 1 year, 5 and 10 years after diagnosis ]
  Show Outcome Measure 4

5.  Secondary:   Long-term Prognosis for Neurologic Recovery by Neurological Examination   [ Time Frame: At diagnosis and yearly for 10 years after diagnosis ]
  Show Outcome Measure 5

6.  Secondary:   Tumor Outcome in Terms of Event-free Survival (EFS) Rate Defined as a Relapse or Progression of Neuroblastoma, a Second Malignancy, or Death   [ Time Frame: Up to 3 years ]
  Show Outcome Measure 6

7.  Secondary:   Tumor Outcome in Terms of Overall Survival (OS) Rate   [ Time Frame: Up to 3 years ]
  Show Outcome Measure 7


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
phone: 626-447-0064
e-mail: resultsreportingcoordinator@childrensoncologygroup.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00033293     History of Changes
Other Study ID Numbers: ANBL00P3
NCI-2009-00399 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000069271 ( Other Identifier: Clinical Trials.gov )
COG-ANBL00P3 ( Other Identifier: Children's Oncology Group )
U10CA013539 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: April 9, 2002
First Posted: January 27, 2003
Results First Submitted: January 28, 2016
Results First Posted: October 3, 2016
Last Update Posted: May 22, 2017