NB2013-HR German (GPOH) / Dutch (DCOG) Trial

Summary

Although the five year survival rate of children with high risk neuroblastoma have increased over the last three decades from 4 to 44 % (1), neuroblastoma is the second most frequent cause for cancer related death in childhood (11 %). Most patients show good initial response rates (complete (CR) and partial remission (PR) rate 95 %), but 55 % experience a largely treatment-resistant tumor progression. Recently, a breakthrough with immunotherapy was reported by US investigators from the Children's Oncology Group (2) using the anti-ganglioside D2 (GD2) monoclonal antibody ch14.18 for tumor cell destruction and granulocyte macrophage-colony stimulating factor (GM-CSF) plus interleukin 2 (IL-2) for immunostimulation. This immune therapy resulted in an increase of 20 % Event free survival (EFS) at 2 year from randomization. However, this was associated with a high toxicity rate (pain, capillary leak syndrome). The proposed trial compares the Childrens' Oncology Group (COG) "standard of care" arm (anti-GD2 + GM-CSF + IL-2 i.v. + retinoic acid oral) with an experimental arm (anti-GD2 + GM-CSF + IL-2 s.c. + retinoic acid oral) designed to reduce toxicity. The potential benefit from this trial consists of the confirmation that the American trial design is feasible in an independent set of patients with different preceding therapy, at a different time point regarding to immune reconstitution after autologous stem cell transplantation (ASCT), the feasibility of a newly designed immunotherapy (which is hopefully less toxic) and the investigation of immune response parameters. This pilot study is the prerequisite for a consecutive randomized clinical trial comparing two immunotherapeutic approaches in a larger set of patients.

Timeline

Start

2015-11

Primary completion

2016-12-23

Completion

2017-01-30

Publications

• Background Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123.
• Background Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Klingebiel T, Berthold F. Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy. BMC Cancer. 2011 Jan 18;11:21. doi: 10.1186/1471-2407-11-21.
• Results Simon T, Hero B, Faldum A, Handgretinger R, Schrappe M, Niethammer D, Berthold F. Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol. 2004 Sep 1;22(17):3549-57. doi: 10.1200/JCO.2004.08.143.

Drugs

Indications