Recurrent, progressive or newly diagnosed high risk neuroblastoma MedDRA version: 17.1 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: chimeric monoclonal antibody 14.18
Product Code: ch14.18
Pharmaceutical Form: Solution for infusion
Trade Name: Leukine
Product Name: Leukine
Pharmaceutical Form: Powder for solution fo
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Established diagnosis of neuroblastoma according to the international INSS criteria High risk (HR): stage 4 over 18 months of age and MYCN amplified neuroblastoma of any stage and any age - Recurrent or progressive neuroblastoma: completed re-induction chemotherapy (Germany and The Netherlands) - Newly diagnosed neuroblastoma: Complete front-line treatment including induction chemotherapy, surgical removal and/ or local irradiation of the primary tumor and myeloablative chemotherapy with autologous stem cell reinfusion according to the actual guidelines of the GPOH/ DCOG (in The Netherlands only). Achieved response status: stable disease or better (CR, VGPR, PR, SD) at the end of re-induction chemotherapy in recurrent disease and after ASCT in newly diagnosed disease Written informed consent of parents or guardian and – if appropriate – of the patient. For at least two weeks prior to start of trial medication - off any standard or experimental treatment (and fully recovered from short-term major toxic effects) - no tumour surgery (and fully recovered from any post-surgical complications) - no immediate requirements for palliative chemotherapy, radiotherapy or surgery The patient may have had prior CNS metastases provided the following criteria are all met: - The patient’s CNS disease has been previously treated - The patient’s CNS disease has been clinically stable for four weeks prior to starting this study (assessed clinically and by MRI or CT) - The patient is off steroids for four weeks prior to starting the study and will not require them during the course of the study - A patient with seizure disorders may be enrolled if well controlled on anticonvulsants and if no seizures have occurred within a 6 week period prior to starting trial treatment HIV sero-negative and neither active nor chronic-replicative hepatitis B infection adequate functions of the cor, lung, bone marrow, liver, kidney Are the trial subjects under 18? yes Number of subjects for this age range: 36 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 2 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Significant intercurrent illnesses and/or any of the following: - Symptoms of congestive heart failure or of uncontrolled cardiac arrhythmia - Significant psychiatric disabilities or psychological conditions preventing treatment realization - Uncontrolled seizure disorders - Active infections - Clinically significant neurologic deficit or objective peripheral neuropathy (> grade 2) - Significant, symptomatic pleural effusions Requirement or likely requirement for corticosteroids or other immunosuppressive drugs (except the medications recommended for conditions mentioned in the protocol) Platelet transfusion dependency Concurrent treatment with any non-trial anticancer therapy or interventional study Positive pregnancy test, lactation Sexually active patients (male and female) at reproductive age not willing to use highly effective contraceptive methods according to the guidelines ICH M3 Neuroblastoma patients with actively progressing disease Patients with HACA detected after previous antiGD2 immunotherapy Known allergy or contraindications against one of the study drugs (IMP)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary trial objective is the safety and tolerability of the two immunotherapy regimens for patients with recurrent high risk neuroblastoma and of the standard immunotherapy regimen for newly diagnosed high risk neuroblastoma (three arm trial). ;Secondary Objective: Reduction of grade 2-4 key side effects in the experimental arm. Neuralgia (with assessment of pain duration (days requiring morphin) and maximum grade of pain scores during first 2 antibody cycles) Comparison of pharmacokinetics of antibody ch14.18 in both arms. Comparison of immune response between treatment cycles, treatment arms and between recurrent and newly diagnosed patients. Comparison of grade 2-4 toxicities between intravenously and subcutaneously administered IL-2. 2 year event free (EFS), progression free (PFS), and overall survival rates (OS) from time of randomization. Tumor response at the end of treatment and time to progression (TTP) Quality of Life (QoL) ;Primary end point(s): Safety (toxic deaths) and tolerability (grade 4 toxicities) for the three treatment arms.;Timepoint(s) of evaluation of this end point: continously during treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: continously resp. at several time-points during treatment (side effects, neuralgia, pharmacokinetics, immune response) at 2 years (EFS, PFS, OS) at end of treamtent (tumor response) at progression (TTP) ;Secondary end point(s): Reduction of grade 2-4 key side effects in the experimental arm. Neuralgia (with assessment of pain duration (days requiring morphin) and maximum grade of pain scores during first 2 antibody cycles) Comparison of pharmacokinetics of antibody ch14.18 in both arms. Comparison of immune response between treatment cycles, treatment arms and between recurrent and newly diagnosed patients. Comparison of grade 2-4 toxicities between intravenously and subcutaneously administered IL-2. 2 year event free (EFS), progression free (PFS), and overall survival rates (OS) from time of randomization. Tumor response at the end of treatment and time to progression (TTP) Quality of Life (QoL) | — |
Countries
Germany, Netherlands
Contacts
Public ContactNeuroblastomstudie
Paediatric Oncology and Haematology
Outcome results
None listed