Haploidentical Stem Cell Transplantation in Neuroblastoma

• ClinicalTrials.gov Identifier: NCT00790413
• Recruitment Status: Active, not recruiting
• First Posted: November 13, 2008
• Last Update Posted: February 21, 2021
• Sponsor: Lund University Hospital
• Information provided by (Responsible Party): Jacek Toporski, Lund University Hospital

Tracking Information

• First Submitted Date: November 12, 2008
• First Posted Date: November 13, 2008
• Last Update Posted Date: February 21, 2021
• Study Start Date: August 2005
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 12, 2008): Engraftment rate [ Time Frame: day 100 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroblastoma

Intervention

• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 12, 2008): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT00790413
• Other Study ID Numbers: 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: Lund University Hospital
• Collaborators: Not Provided

Investigators

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

• PRS Account: Lund University Hospital
• Verification Date: February 2021