Haploidentical Stem Cell Transplantation in Neuroblastoma

Tracking Information
First Submitted Date ICMJE	November 12, 2008
First Posted Date ICMJE	November 13, 2008
Last Update Posted Date	March 14, 2017
Study Start Date ICMJE	August 2005
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 12, 2008)	Engraftment rate [ Time Frame: day 100 ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00790413 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 12, 2008)	Overall survival [ Time Frame: 1 year ]; Immunological reconstitution [ Time Frame: day 100 ]; Incidence of acute graft versus host disease [ Time Frame: day 100 ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Haploidentical Stem Cell Transplantation in Neuroblastoma
Official Title ICMJE	High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Early Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Neuroblastoma
Intervention ICMJE	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
Study Arms	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
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: November 12, 2008)	15
Original Estimated Enrollment ICMJE	Same as current
Study Completion Date	Not Provided
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	6 Months to 21 Years (Child, Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Sweden
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00790413
Other Study ID Numbers ICMJE	385/2005
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Jacek Toporski, Lund University Hospital
Study Sponsor ICMJE	Lund University Hospital
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Jacek Toporski, MD, PhD Lund University Hospital, Department of Pediatric Oncology
PRS Account	Lund University Hospital
Verification Date	March 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP