High-risk neuroblastoma MedDRA version: 16.1 Level: PT Classification code 10029260 Term: Neuroblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Dinutuximab
Product Code: Ch14.18
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: DINUTUXIMAB
Other descriptive name: DINUTUXIMAB
Concentration unit: mg/ml milligram(s)/m
Sponsors
Fundació Sant Joan de Deu de Barcelona
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of neuroblastoma as defined by international criteria by histopathology or bone marrow metastases. 2. Neuroblastoma, as defined by risk-related treatment guidelines and the International Neuroblastoma Staging System, stage 4 with (any age) or without (>18 months) MYCN-amplification, or MYCN-amplified neuroblastoma other than stage 1, or high-risk neuroblastoma defined based on the 3-gene molecular profile. Group 1 patients have neuroblastoma (as defined above) resistant to standard therapy, as evidenced by incomplete response in bone marrow, but no MIBG-avid soft tissue or bone tumor and no progressive disease. Group 2 patients have no evidence of measurable disease, i.e., are in CR/VGPR from neuroblastoma (as defined above). 3. Signed informed consent indicating awareness of the investigational nature of this program. Are the trial subjects under 18? yes Number of subjects for this age range: 10 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: 1. Existing severe major organ dysfunction, i.e., renal., cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity >/= grade 3. 2. Progressive disease or MIBG-avid soft tissue/bone tumor. 3. Active life-threatening infection. 4. Inability to comply with protocol requirements. 5. Patient is elegible for SIOP HR-NB-01 protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate safety of the triple COG immunotherapy schema with the monoclonal antibody Dinutuximab + cytokines (GM-CSF and IL2) and isotretinoin (13-cis-retinoic acid, or RA) in patients with high-risk neuroblastoma who have achieved a CR or VGPR of the macroscopic disease in our institution.;Secondary Objective: To assess response of minimal residual disease (MRD) of the anti-GD2 monoclonal antibody Dinutuximab combined with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-2 in patients with high-risk neuroblastoma (NB). More precisely, to apply real-time quantitative RT-PCR to test the hypothesis that minimal residual disease content of BM after the first treatments with Dinutuximab/GM-CSF has significant prognostic impact on relapse-free survival.;Primary end point(s): Safety, toxicities: The safety and tolerability of the treatment will be determined by means of type, incidence, severity, timing, seriousness, and relatedness; of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 4.0.;Timepoint(s) of evaluation of this end point: Every patient visit, during his/her participation in the clinical trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate of BM response for patients with detectable minimal residual disease in the BM after the first treatment with Dinutuximab/GM-CSF and relation with relapse-free survival. Relapsed-free survival: Defined as the time from the day of start of treatment to the first evidence of progression as defined by International Response Criteria (Brodeur et al., 1993) or death from any cause. If the patient does not have a documented date of progression or death, then PFS will be censored at the date of last adequate assessment.;Timepoint(s) of evaluation of this end point: 1. BM studies at end of cycles 2 and 4 and after the 6th cycle of RA. Subsequently, BM studies are repeated in conjunction with MIBG or PET scan through 2 years in patients with history of BM or cortical bone involvement, but are repeated ~every 6 months in other patients (e.g., patients who were stage 4 by virtue of metastases in distant lymph nodes). 2. CT or MRI of primary site approximately every 3 months through 1 year. 3. 99mTc-MDP-bone approximately every 3 months while on study until normal. 4. MIBG or PET scan approximately every 3 months through 2 years. | — |
Countries
Spain
Contacts
Public ContactDpto Investigacion
MFAR
Outcome results
None listed