Haploidentical Stem Cell Transplantation in Neuroblastoma

Study Overview
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Brief Summary
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Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.

Official Title
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High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma

Conditions
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Neuroblastoma

Intervention / Treatment
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* Drug: iodine I 131 metaiodobenzylguanidine
* Drug: Fludarabine
* Drug: Thiotepa
* Procedure: T-cell depletion
* Procedure: Haploidentical stem cell transplantation
* Procedure: Donor Lymphocyte Infusion
* Drug: Rituximab
* Procedure: Co-transplantation of mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory neuroblastoma (any chemo/radiosensitive stable disease) Relapse incl. autologous HSCT 3 m earlier Primary induction failure Cardiac output SF ≥25% Creatinine clearance ≥40 cc/min/1.73 m2 Performance score of ≥50% (Lansky or Karnofsky) Available haploidentical family donor, aged ≥18 yrs, HIV-neg Exclusion Criteria: Rapidly progressive disease Pregnancy

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-dose MIBG with haploidentical stem cell transplantation<br>High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft | Drug: iodine I 131 metaiodobenzylguanidine<br> <br> Drug: Fludarabine<br> <br> Drug: Thiotepa<br> <br> Procedure: T-cell depletion<br> <br> Procedure: Haploidentical stem cell transplantation<br> <br> Procedure: Donor Lymphocyte Infusion<br> <br> Drug: Rituximab<br> <br> Procedure: Co-transplantation of mesenchymal stem cells<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment rate |  | day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 1 year | 
| Immunological reconstitution |  | day 100 | 
| Incidence of acute graft versus host disease |  | day 100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Immunotherapy, Hematopoietic Stem Cell Transplantation