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Reduced Intensity Stem Cell Transplantation in Children With Relapsed Neuroblastoma After Autologous Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00793351
Recruitment Status : Completed
First Posted : November 19, 2008
Last Update Posted : October 19, 2016
Sponsor:
Information provided by:
Samsung Medical Center

Tracking Information
First Submitted Date  ICMJE November 17, 2008
First Posted Date  ICMJE November 19, 2008
Last Update Posted Date October 19, 2016
Study Start Date  ICMJE September 2008
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2008)
tumor response, overall survival, event-free survival [ Time Frame: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reduced Intensity Stem Cell Transplantation in Children With Relapsed Neuroblastoma After Autologous Transplantation
Official Title  ICMJE Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-intensity Conditioning in Children With Neuroblastoma Who Have Failed a Prior Autologous Transplantation
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE Procedure: Reduced-intensity allogeneic hematopoietic stem cell transplantation

Treatment Scheme

  • Enrollment - Pre-RIST treatment - RIST
  • 4 cycles of conventional chemotherapy will be given prior to RIST.
  • Surgery will be done whenever possible prior to RIST.
  • Local radiotherapy will be applied whenever possible prior to RIST.
  • topotecan + cyclophosphamide) regimen will be used for pre-RIST conventional chemotherapy.
  • Cyclophosphamide/Fludarabine (CyFlu) regimen will be used as conditioning regimen for matched related or unrelated SCT. CyFlu-ATG regimen will be used as conditioning regimen for mismatched related SCT.
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: November 18, 2008)
25
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00793351
Other Study ID Numbers  ICMJE 2008-08-073
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ki Woong Sung, Samsung Medical Center
Study Sponsor  ICMJE Samsung Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Samsung Medical Center
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP