Haploidentical Stem Cell Transplantation in Neuroblastoma

Lund University Hospital

Status and phase: Unknown; Early Phase 1

Conditions: Neuroblastoma

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00790413

385/2005

Details and patient eligibility

About

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.

Enrollment: 15 estimated patients

Sex: All

Ages: 6 months to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

High-dose MIBG with haploidentical stem cell transplantation

Experimental group

Description:

High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft

Treatment:

Drug: Rituximab

Drug: iodine I 131 metaiodobenzylguanidine

Procedure: T-cell depletion

Drug: Fludarabine

Procedure: Haploidentical stem cell transplantation

Procedure: Co-transplantation of mesenchymal stem cells

Procedure: Donor Lymphocyte Infusion

Drug: Thiotepa