Haploidentical Stem Cell Transplantation in Neuroblastoma
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
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
|
Outcome Measures
Primary Outcome Measures
- Engraftment rate [day 100]
Secondary Outcome Measures
- Overall survival [1 year]
- Immunological reconstitution [day 100]
- Incidence of acute graft versus host disease [day 100]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation | Lund | Sweden | 221 85 |
Sponsors and Collaborators
- Lund University Hospital
Investigators
- Principal Investigator: Jacek Toporski, MD, PhD, Lund University Hospital, Department of Pediatric Oncology
Study Documents (Full-Text)
None provided.More Information
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 385/2005