Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma|
- Overall survival and event-free survival, short-term and long-term toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation [ Time Frame: from 1 year after second high-dose chemotherapy ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2008|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Procedure: tandem high-dose chemotherapy
- Conventional chemotherapy (6 cycles) -> surgery -> conventional chemotherapy (3 cycles) -> first HDCT/ASCR -> second HDCT/ASCR -> Local RT + Retinoic acid + IL-2
- First HDCT/ASCR: CEC regimen
- Second HDCT/ASCR:
TM-TBI (in case of stage 4 neuroblastoma) or TM regimen (in case of stage 3 neuroblastoma)
The prognosis of high-risk neuroblastoma after conventional chemoradiotherapy is generally poor. Therefore, a strategy using high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) has been explored to improve the prognosis of patients with high-risk neuroblastoma. This strategy is based on the hypothesis that dose escalation might improve the survival of children with high-risk neuroblastoma. The results of randomized trials comparing HDCT/ASCR with chemotherapy alone showed a better event-free survival (EFS) in the HDCT/ASCR arm than in the continuous chemotherapy arm. However, the overall EFS was unsatisfactory.
In this context, investigators have examined the efficacy of double or triple tandem HDCT/ASCR to further improve the outcome of high-risk neuroblastoma patients. George et al. carried out a single arm trial of tandem transplantation as consolidation therapy, and reported improved long-term survival (5-year progression-free survival 47%) with acceptable toxicity. Kletzel et al. also conducted a single arm trial of triple tandem transplantation and reported improved survival (3-year EFS 57%). They demonstrated that further dose escalation using sequential HDCT/ASCR might result in further improvements in the survival of patients with high-risk neuroblastoma.
Investigators in the present study also carried out tandem transplantation as consolidation therapy, and reported improved long-term survival (5-year progression-free survival 62%) with acceptable toxicity. However, throughout our previous study, multiple modifications were made in the treatment plan, which resulted in significant variability over time between patients. This variability may create doubt as to whether tandem HDCT/ASCR itself resulted in the improved outcome. In addition, toxic death rate was relatively high (15.4%), although final survival rate was very high (best survival rate ever reported). Therefore, prospective study is needed to evaluate the efficacy and toxicity of tandem HDCT/ASCR.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00793845
|Korea, Republic of|
|Samsung Medical Center|
|Seoul, Korea, Republic of|
|Principal Investigator:||Ki Woong Sung, MD||Samsung Medical Center|