High-risk neuroblastoma patients having received at least one previous high dose treatment followed by stem cell rescue after conventional therapy fulfilling one of the following criteria: • Primary refractory patients with stage 4 disease with at least two lines of treatment prior to HDT/SCT, causing a delay from diagnosis to SCT of over 9 months • Relapse after primary stage 4 disease • Disseminated relapse after primary localized neuroblastoma
Conditions
Interventions
Trade Name: Dinutuximab beta EUSA (Qarziba)
Product Name: Dinutuximab beta EUSA (Qarziba)
Product Code: ch14.18/CHO
Pharmaceutical Form: Infusion
INN or Proposed INN: dinutuximab beta
Other descripti
Sponsors
St. Anna Kinderkrebsforschung/CCRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key inclusion criteria Patients with neuroblastoma >1 and = 21 years of age (age limit for trial cohorts only), having received at least one previous high dose treatment followed by stem cell rescue after conventional therapy to reduce tumour burden fulfilling one of the following criteria: • Primary refractory patients with stage 4 disease with at least two lines of treatment prior to HDT/ASCT, causing a delay from diagnosis to ASCT of over 9 months. (For example, patients who are on the current high-risk SIOPEN trial (HR-NBL-1/SIOPEN) and have completed high-dose treatment but are ineligible for the R2 randomization due to major delays for toxicity). • Relapse after primary stage 4 disease. • Disseminated relapsed neuroblastoma having received ASCT. Patients must have a life expectancy of at least 12 weeks. Patients who received previus treatments with ch14.18 SP2/0 or ch14.18/CHO are eligible if they test negative for human anti-chimeric antibodies (HACA) at screening. Patients who are platelet transfusion dependent are eligible if they adequately respond to platelet transfusion (>20.000/µl) Patients who take topical and local acting immunosuppressive drugs without relevant systemic activity such as cremes, inhalative and immunosuppressive drugs acting on mucoasal membranes are allowed on the trial. A substitute test for patients who can not perform a pulmonary function test was defined in order to assess pulmonary function prior to immunotherapy: Pulse oximetry at room air. Patients with a reading = 94% are eligible. Are the trial subjects under 18? yes Number of subjects for this age range: 444 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Progressive disease and previous treatment with ch14.18/SP2/0 and/or ch14.18/CHO
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To find an improved treatment schedule which reduces the pain-toxicity profile of ch14.18/CHO whilst maintaining immunomodulatory efficacy in patients (1-21 years old) with primary refractory (= 2 lines of conventional treatment) or relapsed neuroblastoma through prolonged continuous infusion in combination with s.c aldesleukin (IL-2). V3: Based on the IL-2 toxicity profile and recent data from the HRNBL1 SIOPEN trial, the study committee decided to evaluate the role of IL-2 for EFS (event free survival) in the LTI setting by randomizing the current standard arm against an ch14.18/CHO only treatment arm (additional randomised question = ARAQ). The use of isotretinoin remains unchanged in both treatment arms;Secondary Objective: To assess pain intensity and relief by appropriate medication with a validated self- report tool. To validate, during the first course, the correlation between activated NK cells and ch14.18/CHO level with ADCC by using MNC and serum from patients on day 15. To determine systemic immune modulation/response resulting from the combined treatment of ch14.18/CHO and s.c. aldesleukin (IL-2) by repeated analysis of NK-cell activation, soluble IL-2 receptor, ADCC, CDC and anti-idiotype activation (HAMA and HACA). To achieve an increase in absolute lymphocyte counts and absolute NK cell numbers after the respective cycles as a measurement of response to s.c. aldesleukin (IL-2). To determine the pharmacokinetics of ch14.18/CHO. To evaluate anti-tumour responses resulting from this treatment regimen through clinical assessments in patients with measurable disease. ;Primary end point(s): The primary endpoint is event free survival calculated from the date of randomisation. The following will be considered as events: - disease progression or relapse, - death from any cause - second neoplasm ;Timepoint(s) of evaluation of this end point: The final analysis will be performed 1 year after the closure of the randomisation. All analyses w | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Biomarkers Response criteria Immunological assessments;Timepoint(s) of evaluation of this end point: Descriptive analysis of serum biomarkers at different time points during treatment will be performed. Response analysis - All patients who complete the first cycle will be considered evaluable for anti-tumour response. | — |
Countries
Australia, Austria, Belgium, France, Germany, Hong Kong, Ireland, Israel, Italy, Poland, Spain, United Kingdom
Contacts
Public ContactRuth Ladenstein
Children's Cancer Research Institute
Outcome results
None listed