Haploidentical Stem Cell Transplantation in Neuroblastoma

Early Phase 1

• Conditions: Neuroblastoma
• Interventions: 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

• Registration Number: NCT00790413
• Lead Sponsor: Lund University Hospital

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-08
• Study First Submitted: 2008-11-12
• Study First Submitted QC: 2008-11-12
• Study First Posted: 2008-11-13
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-17
• Last Update Posted: 2021-02-21
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High-dose MIBG with haploidentical stem cell transplantation	iodine I 131 metaiodobenzylguanidine	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Donor Lymphocyte Infusion	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	T-cell depletion	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Co-transplantation of mesenchymal stem cells	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Haploidentical stem cell transplantation	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Fludarabine	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Thiotepa	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
High-dose MIBG with haploidentical stem cell transplantation	Rituximab	High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft

Primary Outcome Measures

Name	Time	Method
Engraftment rate	day 100

Secondary Outcome Measures

Name	Time	Method
Immunological reconstitution	day 100
Incidence of acute graft versus host disease	day 100
Overall survival	1 year

Trial Locations

Locations (1)

Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation; 🇸🇪 Lund, Sweden