Tandem High Dose Chemotherapy With 131I-MIBG Treatment in High Risk Neuroblastoma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and toxicity of tandem HDCT/ASCT including high-dose 131I-metaiodobenzylguanidine (MIBG) treatment. In the present study, a single arm trial of tandem HDCT/ASCT will be carried out.

Detailed Description
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Although the outcome of high-risk neuroblastoma has improved after the introduction of HDCT/ASCT, the outcome was still unsatisfactory with 30-40% of survival. We previously reported the results of a single arm prospective trial (SMC NB-2004 study) using tandem HDCT/auto-SCT for high-risk neuroblastoma. In the NB-2004 trial, total body irradiation (TBI) was incorporated in second transplantation. Survival rates were very encouraging; however, short- and long-term toxicities associated with tandem HDCT/auto-SCT, particularly TBI, were also very significant. For this reason, we designed a new prospective trial (SMC NB-2009 study), in which only TBI in the second HDCT/auto-SCT of NB-2004 study was substituted with high-dose 131I-MIBG treatment in order to reduce short- and long-term toxicities without jeopardizing survival rate.

Official Title
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High-dose 131I-MIBG Treatment Incorporated Into Tandem High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With High-risk Neuroblastoma

Conditions
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High Risk Neuroblastoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Carboplatin
* Drug: Etoposide
* Radiation: 131I-MIBG
* Drug: Thiotepa
* Drug: Melphalan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with high-risk neuroblastoma Exclusion Criteria: Patients with progressive disease before high-dose chemotherapy Patients whose parents want to stop or change the planned treatment Patients with organ toxicities of NCI grade >2 before high-dose chemotherapy

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High risk neuroblastoma<br>Conventional chemotherapy (9 cycles) Surgery conventional chemotherapy (after 6 cycles of chemotherapy) Tandem HDCT/autoSCT First HDCT (cyclophosphamide, etoposide, carboplatin) Second HDCT (high-dose 131I-MIBG, thiotepa, melphalan) Local radiotherapy Retinoic acid, interleukin-2 | Drug: Cyclophosphamide<br>* 1st HDCT<br>Drug: Carboplatin<br>* 1st HDCT<br>Drug: Etoposide<br>* 1st HDCT<br>Radiation: 131I-MIBG<br>* 2nd HDCT<br>Drug: Thiotepa<br>* 2nd HDCT<br>Drug: Melphalan<br>* 2nd HDCT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of event free survival | Event is defined as relapse, disease progression or treatment-related mortality. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment-related adverse events as assessed by CTCAE v4.0 |  | Up to 5 years |