Haploidentical Stem Cell Transplantation in Neuroblastoma

Sponsor
Lund University Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00790413
Collaborator
(none)
15
Enrollment
1
Location
1
Arm
209
Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • 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
Early Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
Study Start Date :
Aug 1, 2005
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: High-dose MIBG with haploidentical stem cell transplantation

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

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

Outcome Measures

Primary Outcome Measures

  1. Engraftment rate [day 100]

Secondary Outcome Measures

  1. Overall survival [1 year]

  2. Immunological reconstitution [day 100]

  3. Incidence of acute graft versus host disease [day 100]

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Lund University Hospital, Department of Pediatric Oncology and Bone Marrow TransplantationLundSweden221 85

Sponsors and Collaborators

  • Lund University Hospital

Investigators

  • Principal Investigator: Jacek Toporski, MD, PhD, Lund University Hospital, Department of Pediatric Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Jacek Toporski, MD, PhD, Lund University Hospital
ClinicalTrials.gov Identifier:
NCT00790413
Other Study ID Numbers:
  • 385/2005
First Posted:
Nov 13, 2008
Last Update Posted:
Feb 21, 2021
Last Verified:
Feb 1, 2021
Keywords provided by Jacek Toporski, MD, PhD, Lund University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 21, 2021