High Risk Neuroblastoma
Conditions
Interventions
Product Name: chimeric antibody ch14.18/CHO
Product Code: ch14.18/CHO
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: ch14.18/CHO
Other descriptive name: ch
Sponsors
St. Anna Kinderkrebsforschung e.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Established diagnosis of neuroblastoma according to the International Neuroblastoma Staging System (INSS) • Age below 21 years. • High-risk neuroblastoma, defined as either: a) INSS stages 2, 3, 4 and 4s with MYCN amplification, or b) INSS stage 4 without MYCN amplification aged = 12 months • Patients who have received no previous chemotherapy except for 1 cycle of etoposide and carboplatin (Vp/Carbo). In this situation patients will receive Rapid COJEC induction and the first COJEC cycle may be replaced by the first cycle of Vp/Carbo. • Written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met. • Tumour cell material available for determination of biological prognostic factors. • Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis. • Provisional follow up of 5 years. • National and local ethical committee approval. The date of eligibility is defined as the date at which all criteria for entry into the study have been checked by the co-ordinating centre along with the referring physician. The date of diagnosis will be the starting point for subsequent follow up. Are the trial subjects under 18? yes Number of subjects for this age range: 2200 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
Exclusion criteria
Exclusion criteria: Any negative answer concerning the inclusion criteria of the study, R2 and R3 will render the patient ineligible for the corresponding therapy phase.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives •To test the hypothesis that the modified N7 induction regimen will improve the metastatic response or event free survival rate in a higher number of patients as compared to Rapid COJEC. •To test the hypothesis that immunotherapy with chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells (ch14.18/CHO) and subcutaneous aldesleukin (IL-2, (Proleukin®)), following MAT and autologous SCR, in addition to differentiation therapy with isotretinoin (13-cis-RA), will improve 3-year EFS in patients with high-risk neuroblastoma (stage 4 disease or stages 2 and 3 with MYCN amplification all over the age of one, or infants with MYCN amplification). ;Secondary Objective: To evaluate BM response to Rapid COJEC and to modified N7. To evaluate response to Rapid COJEC and modified N7 induction therapies with mIBG for standardised scoring of skeletal response To determine the effect of response of metastatic disease to induction therapy, on EFS and OS To investigate the relationship between complete surgical resection of the primary tumour, and OS To collect data on selected, validated biological features and to determine the effect of these on EFS, the incidence of relapse/progression and OS To compare the toxicity, in particular episodes of febrile neutropenia and grade 3-4 infection associated with induction therapy with Rapid COJEC and modified N7 To sample PK data to calculate the effect of AUC as achieved according to dosing guidelines To monitor drug levels of MAT and to relate them to patients’ outcome and toxicity To collect data on selected, validated biological features and to determine the effect of these on EFS and OS;Primary end point(s): Randomisation 3: Two co-primary endpoints will be investigated: 1)Metastatic response after induction •No skeletal uptake on MIBG •Negative Bone marrow aspirates and trephines •Absence of other metastatic sites 2)Event Free Survival •disease progression or rel | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints of the main trial • Overall survival Calculated from date of randomisation to death from any cause. Patients lost to follow-up without an event will be censored at the date of their last follow-up evaluation. • Cumulative incidence of relapse/progression and deaths without relapse/progression • The cumulative incidence of treatment related mortality and of disease related mortality • Response Overall response (incl. primary tumour after induction), skeletal response on MIBG, BM-response, • Toxicity in particular comparison of the frequency of episodes of febrile neutropenia and grade 3-4 infections during induction (modified N7 vs. Cojec) • Response rates, survival, EFS and the cumulative incidence of relapse/progressions will be related to potential prognostic factors including: - Biological factors (MYCN amplification, SCAs, expression signature) of neuroblastoma cells in the bone marrow and/or the primary tumour. - Serological factors (serum concentrations at diagnosis of LDH, ferritin, neuron specific enolase). - Urinary catecholamines at diagnosis (VMA, HVA, Dopamine) ;Timepoint(s) of evaluation of this end point: The final analysis will be performed 18 months for R1 and R2 and 6 months for R3 after the inclusion of the last patient. | — |
Countries
Australia, Austria, Belgium, Czech Republic, Denmark, Finland, France, Greece, Hungary, Ireland, Israel, Italy, Norway, Poland, Portugal, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactRuth Ladenstein
St. Anna Kinderkrebsforschung
Outcome results
None listed