| November 12, 2008
|
| November 13, 2008
|
| March 14, 2017
|
| August 2005
|
| December 2018 (Final data collection date for primary outcome measure)
|
| Engraftment rate [ Time Frame: day 100 ]
|
| Same as current
|
| Complete list of historical versions of study NCT00790413 on ClinicalTrials.gov Archive Site
|
- Overall survival [ Time Frame: 1 year ]
- Immunological reconstitution [ Time Frame: day 100 ]
- Incidence of acute graft versus host disease [ Time Frame: day 100 ]
|
| Same as current
|
| Not Provided
|
| Not Provided
|
| |
| Haploidentical Stem Cell Transplantation in Neuroblastoma |
| High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma |
| 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. |
| Not Provided |
| Interventional |
| Early Phase 1 |
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment |
| Neuroblastoma |
- 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
|
| 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
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
|
- 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.
- 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.
- 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. Review.
- 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. Epub 2003 Sep 18.
- 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.
- Lang P, Pfeiffer M, Müller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Föll 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.
- Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Békássy 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.
|
| |
| Active, not recruiting |
| 15 |
| Not Provided |
| December 2018 (Final data collection date for primary outcome measure) |
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
|
| Sexes Eligible for Study: |
All |
|
| 6 Months to 21 Years (Child, Adult) |
| No |
| Contact information is only displayed when the study is recruiting subjects |
| Sweden |
| |
| |
| NCT00790413 |
| 385/2005 |
| Not Provided |
| Not Provided |
| Not Provided |
| Jacek Toporski, Lund University Hospital |
| Lund University Hospital |
| Not Provided |
| Principal Investigator: |
Jacek Toporski, MD, PhD |
Lund University Hospital, Department of Pediatric Oncology |
|
| Lund University Hospital |
| March 2017 |
