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

This study has been completed.

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

ClinicalTrials.gov Identifier:

NCT00033293

First received: April 9, 2002

Last updated: April 18, 2017

Last verified: June 2015

History of Changes

Results First Received: January 28, 2016

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

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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.

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

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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.
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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

Description

Arm I (Chemotherapy, Immunoglobulin Therapy)

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

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1. Primary:

Number of Responders [ Time Frame: Changes from baseline to 2 months, 6 months, and 1 year ]

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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 ]

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5. Secondary:

Long-term Prognosis for Neurologic Recovery by Neurological Examination [ Time Frame: At diagnosis and yearly for 10 years after diagnosis ]

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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 ]

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7. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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
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More Information

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Must obtain prior Sponsor approval

Results Point of Contact:

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

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 )
Study First Received:	April 9, 2002
Results First Received:	January 28, 2016
Last Updated:	April 18, 2017

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