NCT00790413

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at P25-P50 for early_phase_1

Timeline
Completed

Started Aug 2005

Longer than P75 for early_phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2005

Completed
3.3 years until next milestone

First Submitted

Initial submission to the registry

November 12, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 13, 2008

Completed
14.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

February 21, 2021

Status Verified

February 1, 2021

Enrollment Period

17.4 years

First QC Date

November 12, 2008

Last Update Submit

February 17, 2021

Conditions

Neuroblastoma

Keywords

RadiotherapyImmunotherapyHematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

  • Engraftment rate

    day 100

Secondary Outcomes (3)

  • Overall survival

    1 year

  • Immunological reconstitution

    day 100

  • Incidence of acute graft versus host disease

    day 100

Study Arms (1)

High-dose MIBG with haploidentical stem cell transplantation

EXPERIMENTAL

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

Drug: iodine I 131 metaiodobenzylguanidineDrug: FludarabineDrug: ThiotepaProcedure: T-cell depletionProcedure: Haploidentical stem cell transplantationProcedure: Donor Lymphocyte InfusionDrug: RituximabProcedure: Co-transplantation of mesenchymal stem cells

Interventions

iodine I 131 metaiodobenzylguanidineDRUG
High-dose MIBG with haploidentical stem cell transplantation
FludarabineDRUG
High-dose MIBG with haploidentical stem cell transplantation
ThiotepaDRUG
High-dose MIBG with haploidentical stem cell transplantation
T-cell depletionPROCEDURE
High-dose MIBG with haploidentical stem cell transplantation
Haploidentical stem cell transplantationPROCEDURE
High-dose MIBG with haploidentical stem cell transplantation
Donor Lymphocyte InfusionPROCEDURE
High-dose MIBG with haploidentical stem cell transplantation
RituximabDRUG
High-dose MIBG with haploidentical stem cell transplantation
Co-transplantation of mesenchymal stem cellsPROCEDURE
High-dose MIBG with haploidentical stem cell transplantation

Eligibility Criteria

Age6 Months - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • Rapidly progressive disease
  • Pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation

Lund, 221 85, Sweden

Location

Related Publications (8)

  • Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, Sakata N, Yasui M, Okamura T, Kawa K. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003 Jul;32(1):103-6. doi: 10.1038/sj.bmt.1704070.

    PMID: 12815485BACKGROUND

  • Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.

    PMID: 16421427BACKGROUND

  • Prigione I, Corrias MV, Airoldi I, Raffaghello L, Morandi F, Bocca P, Cocco C, Ferrone S, Pistoia V. Immunogenicity of human neuroblastoma. Ann N Y Acad Sci. 2004 Dec;1028:69-80. doi: 10.1196/annals.1322.008.

    PMID: 15650233BACKGROUND

  • Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Hank JA, Surfus J, Dixon JR, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2004 Jan;53(1):41-52. doi: 10.1007/s00262-003-0435-2. Epub 2003 Sep 18.

    PMID: 14504825BACKGROUND

  • Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V. Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene. 2005 Jul 7;24(29):4634-44. doi: 10.1038/sj.onc.1208594.

    PMID: 15897905BACKGROUND

  • Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Foll J, Martin D, Handgretinger R. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006 Nov-Dec;218(6):321-6. doi: 10.1055/s-2006-942256.

    PMID: 17080334BACKGROUND

  • Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Bekassy AN. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. Biol Blood Marrow Transplant. 2009 Sep;15(9):1077-85. doi: 10.1016/j.bbmt.2009.05.007. Epub 2009 Jul 8.

    PMID: 19660720RESULT

  • Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, Schwarze CP, Holzer U, Lode HN, Albert MH, Gruhn B, Urban C, Dykes JH, Teuffel O, Schumm M, Handgretinger R, Lang P. Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma. Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012. doi: 10.1016/j.bbmt.2017.12.805. Epub 2018 Jan 4.

    PMID: 29307718RESULT

MeSH Terms

Conditions

Neuroblastoma

Interventions

3-IodobenzylguanidinefludarabineThiotepaRituximab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

GuanidinesAmidinesOrganic ChemicalsIodobenzenesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsHydrocarbons, IodinatedHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsTriethylenephosphoramideAziridinesAzirinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Jacek Toporski, MD, PhD

    Lund University Hospital, Department of Pediatric Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

November 12, 2008

First Posted

November 13, 2008

Study Start

August 1, 2005

Primary Completion

December 31, 2022

Study Completion

December 31, 2022

Last Updated

February 21, 2021

Record last verified: 2021-02

Locations

SE(1)