Ignite Creation Date:
2024-05-06 @ 7:59 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02641782
Status:
TERMINATED
Last Update Posted:
2022-11-04
First Post:
2015-12-12
Brief Title:
NB2013-HR German GPOH Dutch DCOG Trial
Sponsor:
University of Cologne
Organization:
University of Cologne
Study Overview
Official Title:
Randomized Phase 2 Trial Comparing Experimental Immunotherapy in Recurrent High Risk Neuroblastoma Patients With Standard Immunotherapy in Patients With Recurrent and Newly Diagnosed High Risk Neuroblastoma
Status:
TERMINATED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Antibody supply was discontinued by United Therapeutics Corporation
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NB2013-HR
Brief 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 Childrens Oncology Group 2 using the anti-ganglioside D2 GD2 monoclonal antibody ch1418 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 iv retinoic acid oral with an experimental arm anti-GD2 GM-CSF IL-2 sc 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
Recently a breakthrough with immunotherapy was reported by US investigators from the Childrens Oncology Group 2 using the anti-ganglioside D2 GD2 monoclonal antibody ch1418 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 iv retinoic acid oral with an experimental arm anti-GD2 GM-CSF IL-2 sc 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
Detailed Description:
Neuroblastoma is the second most frequent solid tumour 76 and the second cause of cancer related death 11 in childhood In particular the large high risk HR group has remained a challenge to Paediatric Oncologists Although the 5 year survival rates of children with HR disease have increased over the last 3 decades from 4 to 444 the vast majority of those children will finally succumb to disease 1 Most patients show good initial responses to chemotherapy CR PR-rate 95 but a majority experiences a highly treatment resistant tumour progression 55 Therefore new therapeutic modalities are urgently needed
Recently a randomized trial demonstrated that an immunotherapeutic concept using the anti-GD2 antibody ch1418 together with interleukin 2 GM-CSF and retinoic acid improved the outcome of neuroblastoma patients which achieved CR or very good partial remission VGPR response to the preceding therapy This treatment was associated with a high rate of toxic effects neuropathic pain 52 of patients capillary leak syndrome 23 An earlier study using the antibody ch1418 alone made comparable observations pain despite of analgesia was seen in 33 of patients and severe capillary leak syndromes in 3 of 151 children Differences of the reported frequencies are due to the different definitions of side effects
The investigators therefore propose a randomized clinical trial comparing the COG immunotherapy concept with newly designed hopefully equally effective but less toxic concept This modifies the application route of IL-2 from iv to sc and increases the IL-2 dose to 60 miom²xd from 30 first week and 45 mio second week iv Oral retinoic acid is used in both arms The proposed randomized trial will answer the following questions
i Confirmation of the feasibility to apply the COG immunotherapy as consolidation treatment after a different remission induction therapy in patients with recurrent and de novo high risk neuroblastoma ii Investigation of the feasibility to apply the new immunotherapy concept in patients with recurrent high risk neuroblastoma iii Comparison of the toxicity of both immunotherapy regimens with the aim to reduce grade 2 - 4 toxicities in the experimental arm
iv Comparison of the immune response antiidiotype antibodies immune cell phenotypes immune mediators functional assays as antibody dependent cellular cytotoxicity ADCC and complement dependent cytotoxicity CDC between treatment cycles intraindividual treatment arms interindividual and between recurrent and newly diagnosed patients v Comparison of pharmacokinetics of antibody ch1418 in both arms 1210 vi Comparison of therapeutic efficacy by response evaluation at the end of the 25 week treatment descriptive
vii Comparison of patients QoL experienced in both immunotherapy regimens as indicated by parents rating in appropriate questionnaires
Recently a randomized trial demonstrated that an immunotherapeutic concept using the anti-GD2 antibody ch1418 together with interleukin 2 GM-CSF and retinoic acid improved the outcome of neuroblastoma patients which achieved CR or very good partial remission VGPR response to the preceding therapy This treatment was associated with a high rate of toxic effects neuropathic pain 52 of patients capillary leak syndrome 23 An earlier study using the antibody ch1418 alone made comparable observations pain despite of analgesia was seen in 33 of patients and severe capillary leak syndromes in 3 of 151 children Differences of the reported frequencies are due to the different definitions of side effects
The investigators therefore propose a randomized clinical trial comparing the COG immunotherapy concept with newly designed hopefully equally effective but less toxic concept This modifies the application route of IL-2 from iv to sc and increases the IL-2 dose to 60 miom²xd from 30 first week and 45 mio second week iv Oral retinoic acid is used in both arms The proposed randomized trial will answer the following questions
i Confirmation of the feasibility to apply the COG immunotherapy as consolidation treatment after a different remission induction therapy in patients with recurrent and de novo high risk neuroblastoma ii Investigation of the feasibility to apply the new immunotherapy concept in patients with recurrent high risk neuroblastoma iii Comparison of the toxicity of both immunotherapy regimens with the aim to reduce grade 2 - 4 toxicities in the experimental arm
iv Comparison of the immune response antiidiotype antibodies immune cell phenotypes immune mediators functional assays as antibody dependent cellular cytotoxicity ADCC and complement dependent cytotoxicity CDC between treatment cycles intraindividual treatment arms interindividual and between recurrent and newly diagnosed patients v Comparison of pharmacokinetics of antibody ch1418 in both arms 1210 vi Comparison of therapeutic efficacy by response evaluation at the end of the 25 week treatment descriptive
vii Comparison of patients QoL experienced in both immunotherapy regimens as indicated by parents rating in appropriate questionnaires
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None