NeuroblastomaPhase 2NCT00793351
Reduced Intensity Stem Cell Transplantation in Children With Relapsed Neuroblastoma After Autologous Transplantation
A Phase 2 study testing Reduced-intensity allogeneic hematopoietic stem cell transplantation in people with Neuroblastoma, run by Samsung Medical Center at 1 site in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 20 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Reduced-intensity allogeneic hematopoietic stem cell transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 25 participants
- Where
- 1 siteSouth Korea
- Study dates
- Sep 2008to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-intensity Conditioning in Children With Neuroblastoma Who Have Failed a Prior Autologous Transplantation
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.
Read the 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.
- Conditions
- Neuroblastoma
- Being tested
- Reduced-intensity allogeneic hematopoietic stem cell transplantation
- Keywords
- reduced intensity stem cell transplantation for neuroblastoma, relapsed neuroblastoma after high-dose chemotherapy and autologous stem cell rescue
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced-intensity allogeneic hematopoietic stem cell transplantationProcedure or surgery
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
tumor response, overall survival, event-free survival
Measured: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startSep 2008
- Primary completionNov 2013
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793351
- Sponsor's protocol ID
- 2008-08-073
- Status last verified
- Nov 2015
- First submitted
- 17 Nov 2008
- Last updated
- 19 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Stem Cell Transplantation With Reduced-intensity Conditioning in Children With Neuroblastoma Who Have Failed a Prior Autologous Transplantation
- ClinicalTrials.gov ID
- NCT00793351
- Acronym / sponsor ID
- 2008-08-073
- Conditions
- Neuroblastoma
- Keywords
- reduced intensity stem cell transplantation for neuroblastoma, relapsed neuroblastoma after high-dose chemotherapy and autologous stem cell rescue
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 19 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced-intensity allogeneic hematopoietic stem cell transplantationTreatment 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. | Procedure or surgery | – |
Primary outcome
tumor response, overall survival, event-free survival
Time frame: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
Related trials for Neuroblastoma
RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
Active, not recruitingObservational study
Genomic Structural Variation in Cancer Susceptibility
Breast Cancer, Colon Cancer
RecruitingPhase 2
Enasidenib in IDH2-Mutated Malignant Sinonasal and Skull Base Tumors
Metastatic Chondrosarcoma, Locally Advanced Chondrosarcoma
RecruitingObservational study
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms
Endocrine Tumors, Thyroid Neoplasms
RecruitingPhase 1
PEACH TRIAL- Precision Medicine and Adoptive Cellular Therapy
Neuroblastoma, Diffuse Intrinsic Pontine Glioma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Reduced-intensity allogeneic hematopoietic stem cell transplantation in people with Neuroblastoma, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
tumor response, overall survival, event-free survival (time frame: from 1 year after reduced-intensity allogeneic hematopoietic stem cell transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2016.