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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by Samsung Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT00793351
First received: November 17, 2008
Last updated: May 23, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Procedure: Reduced-intensity allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-intensity Conditioning in Children With Neuroblastoma Who Have Failed a Prior Autologous Transplantation

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • tumor response, overall survival, event-free survival [ Time Frame: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: September 2008
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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.

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793351

Contacts
Contact: Ki Woong Sung 82-2-3410-3529 kwsped@skku.edu

Locations
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Ki Woong Sung    82-2-3410-3529    kwsped@skku.edu   
Principal Investigator: Ki Woong Sung         
Sponsors and Collaborators
Samsung Medical Center
  More Information

No publications provided

Responsible Party: Ki Woong Sung, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT00793351     History of Changes
Other Study ID Numbers: 2008-08-073
Study First Received: November 17, 2008
Last Updated: May 23, 2011
Health Authority: South Korea: Institutional Review Board

Keywords provided by Samsung Medical Center:
reduced intensity stem cell transplantation for neuroblastoma
relapsed neuroblastoma after high-dose chemotherapy and autologous stem cell rescue

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on July 20, 2014