Haploidentical Stem Cell Transplantation in Neuroblastoma
Primary Purpose
Neuroblastoma
Status
Unknown status
Phase
Early Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
iodine I 131 metaiodobenzylguanidine
Fludarabine
Thiotepa
T-cell depletion
Haploidentical stem cell transplantation
Donor Lymphocyte Infusion
Rituximab
Co-transplantation of mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma focused on measuring Radiotherapy, Immunotherapy, Hematopoietic Stem Cell Transplantation
Eligibility Criteria
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
Sites / Locations
- Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
High-dose MIBG with haploidentical stem cell transplantation
Arm Description
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
Outcomes
Primary Outcome Measures
Engraftment rate
Secondary Outcome Measures
Overall survival
Immunological reconstitution
Incidence of acute graft versus host disease
Full Information
NCT ID
NCT00790413
First Posted
November 12, 2008
Last Updated
February 17, 2021
Sponsor
Lund University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00790413
Brief Title
Haploidentical Stem Cell Transplantation in Neuroblastoma
Official Title
High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 2005 (undefined)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Lund University Hospital
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
Radiotherapy, Immunotherapy, Hematopoietic Stem Cell Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High-dose MIBG with haploidentical stem cell transplantation
Arm Type
Experimental
Arm Description
High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft
Intervention Type
Drug
Intervention Name(s)
iodine I 131 metaiodobenzylguanidine
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Intervention Type
Procedure
Intervention Name(s)
T-cell depletion
Intervention Type
Procedure
Intervention Name(s)
Haploidentical stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
Donor Lymphocyte Infusion
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Type
Procedure
Intervention Name(s)
Co-transplantation of mesenchymal stem cells
Primary Outcome Measure Information:
Title
Engraftment rate
Time Frame
day 100
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
1 year
Title
Immunological reconstitution
Time Frame
day 100
Title
Incidence of acute graft versus host disease
Time Frame
day 100
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacek Toporski, MD, PhD
Organizational Affiliation
Lund University Hospital, Department of Pediatric Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
12815485
Citation
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.
Results Reference
background
PubMed Identifier
16421427
Citation
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.
Results Reference
background
PubMed Identifier
15650233
Citation
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.
Results Reference
background
PubMed Identifier
14504825
Citation
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.
Results Reference
background
PubMed Identifier
15897905
Citation
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.
Results Reference
background
PubMed Identifier
17080334
Citation
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.
Results Reference
background
PubMed Identifier
19660720
Citation
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.
Results Reference
result
PubMed Identifier
29307718
Citation
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.
Results Reference
result
Learn more about this trial
Haploidentical Stem Cell Transplantation in Neuroblastoma
We'll reach out to this number within 24 hrs