Haploidentical Stem Cell Transplantation in Neuroblastoma - Full Text View

Purpose

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	Intervention	Phase
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	Phase 0


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

MedlinePlus related topics: Neuroblastoma

Drug Information available for: Thiotepa Fludarabine Fludarabine phosphate Rituximab

Genetic and Rare Diseases Information Center resources: Neuroblastoma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Lund University Hospital:

Primary Outcome Measures:

Engraftment rate [ Time Frame: day 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Immunological reconstitution [ Time Frame: day 100 ] [ Designated as safety issue: Yes ]
Incidence of acute graft versus host disease [ Time Frame: day 100 ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	15
Study Start Date:	August 2005
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	6 Months to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790413

Locations


Sweden
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

More Information

Publications:

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.

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.


Responsible Party:	Jacek Toporski, MD, PhD, Head, Section of Pediatric Oncology/Hematology, Lund University Hospital
ClinicalTrials.gov Identifier:	NCT00790413 History of Changes
Other Study ID Numbers:	385/2005
Study First Received:	November 12, 2008
Last Updated:	March 3, 2016
Health Authority:	Sweden: Regional Ethical Review Board

Keywords provided by Lund University Hospital:


Radiotherapy Immunotherapy Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:


Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Fludarabine Fludarabine phosphate Rituximab Thiotepa	3-Iodobenzylguanidine Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists Enzyme Inhibitors Radiopharmaceuticals

ClinicalTrials.gov processed this record on September 29, 2016