Overview

This trial is active, not recruiting.

Condition neuroblastoma
Treatment reduced-intensity allogeneic hematopoietic stem cell transplantation
Phase phase 2
Sponsor Samsung Medical Center
Start date September 2008
End date March 2014
Trial size 25 participants
Trial identifier NCT00793351, 2008-08-073

Summary

The purpose of this study is to evaluate the feasibility and efficacy of reduced-intensity allogeneic stem cell transplantation (RIST) with RIC regimen in children with neuroblastoma who have failed a prior autologous stem cell transplantation. The investigators will investigate the potential of RIC regimen in inducing antitumor response if the present protocol will indeed reduce the early TRM and allow for sustained donor chimerism.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
tumor response, overall survival, event-free survival
time frame: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation

Eligibility Criteria

Male or female participants up to 20 years old.

Inclusion Criteria: - Patients with NB who have failed a prior auto-SCT will be eligible for the present study. Patients should have no severe comorbid organ dysfunction (NCI grade > 2 organ toxicity) at enrollment. Exclusion Criteria: - Patients with severe comorbid organ dysfunction (NCI grade > 2 organ toxicity) prior to RIST will be off the present study. - Patients with progressed tumor prior to RIST will be off the present study. - Patients whose parents do not want to undergo RIST will be off the present study.

Additional Information

Official title Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-intensity Conditioning in Children With Neuroblastoma Who Have Failed a Prior Autologous Transplantation
Description The prognosis of high-risk neuroblastoma (NB) after conventional chemoradiotherapy is very poor. Therefore, a strategy using high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) has been explored to improve the prognosis of patients with high-risk NB. The results of randomized trials comparing HDCT/auto-SCT with chemotherapy alone showed a better event-free survival (EFS) in the auto-SCT arm than in the continuous chemotherapy arm. However, the overall EFS was still unsatisfactory. In this context, investigators have examined the efficacy of double or triple tandem auto-SCT to further improve the outcome of high-risk NB patients. George et al. carried out a single arm trial of tandem auto-SCT 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 auto-SCT and reported improved survival (3-year EFS 57%). Investigators in the present study also carried out tandem auto-SCT as consolidation therapy, and reported improved long-term survival (5-year progression-free survival 62%) with acceptable toxicity. However, unfortunately, tumor relapses in many patients even after tandem auto-SCT. The major cause of treatment failure following auto-SCT remains relapse of the underlying disease. Additional chemotherapy after relapse in these patients have been ineffective, and therefore, new treatment strategies are warranted. In this context, allogeneic stem cell transplantation (allo-SCT) has been tried as salvage treatment in patients with NB who have failed a prior auto-SCT. Allo-SCT would theoretically be preferable in term of relapse-free survival because this has an antitumor effect due to a graft versus tumor (GVT) effect which is absent in auto-SCT. The graft versus leukemia (GVL) effect represents a widely accepted major component of allo-SCT, and there is emerging evidence also for a GVT effect in solid tumor. GVT effect was also demonstrated in patient with advanced NB who received HLA haplo-identical allo-SCT. Generally, allo-SCT carries a lower risk of relapse, However, it has a much higher early treatment-related mortality (TRM) compared to auto-SCT. TRM rate in allo-SCT is especially high in patients who have failed a prior auto-SCT. The 1-year TRM rate following a conventional (ie myeloablative) allo-SCT in adult recipients of a prior auto-SCT has been reported as high as 50-85%. In children, transplantation-related toxicity was also one of the major obstacles in conventional allo-SCT because they had been already heavily treated prior to allo-SCT. Therefore, this salvage strategy has showed a limited success in the majority of children with relapsed NB who have failed a prior single or tandem auto-SCT, although allo-SCT is supposed to be the only curative treatment in patients. Only a small proportion of these patients have the opportunity to successfully undergo this treatment. In recent years, several groups of investigators have developed non-myeloablative reduced-intensity conditioning (RIC) regimen, which lead to engraftment of donor lymphoid and hematopoietic stem cells without the extra-hematopoietic toxicities of traditional myeloablative transplantations while conserving the GVL or GVT effect after transplantation. This reduced toxicity may make these RIC regimens especially suitable for patients with high-risk of TRM, in particular recipients of second or third transplantation.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Samsung Medical Center.