Neuroblastoma
Conditions
Keywords
Antibody, Neuroblastoma, Pediatric, Adult
Brief summary
Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone and/or bone marrow will be treated for up to 101 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Patients will be followed for up to five years after first dose. Naxitamab, also known as hu3F8 is a humanised monoclonal antibody targeting GD2
Detailed description
Each patient will receive treatment for up to 101 weeks following the first Naxitamab administration. After the end of trial visit, each patient will enter a long-term follow-up where they will be monitored for up to 5 years after first treatment cycle. Each investigational cycle is started with 5 days, days -4 to 0, of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) administered at 250 µg/m2/day in advance of the start of Naxitamab administration. GM-CSF is thereafter administered at 500 µg/m2/day on days 1 to 5. As standard treatment, Naxitamab is administered at 3 mg/kg/day on days 1, 3, and 5, totalling 9 mg/kg per cycle. Treatment cycles are repeated every 4 weeks (±1 week) until complete response or partial response followed by 5 additional cycles every 4 weeks (±1 week). Subsequent cycles are repeated every 8 weeks (±2 weeks) through 101 weeks from first infusion at the discretion of the investigator. End of treatment will take place around 8 weeks after the last cycle and thereafter long-term follow-up will continue.
Interventions
BIOLOGICALGM-CSF + Naxitamab
Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody
Sponsors
Y-mAbs Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will receive cycles of GM-CSF and Naxitamab every 4 weeks up to a total of 101 weeks. Safety and efficacy will be investigated with short-term follow-up at minimum 4 weeks after last treatment and with long-term follow-up for up to 3 years after end of treatment visit.
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of neuroblastoma as defined per International Neuroblastoma Response Criteria * High-risk neuroblastoma patients with either primary refractory disease or incomplete response to salvage treatment (in both cases including stable disease, minor response and partial response) evaluable in bone and/or bone marrow. * Life expectancy ≥ 6 months
Exclusion criteria
* Any systemic anti-cancer therapy, including chemotherapy or immunotherapy, within 3 weeks before 1st dose of GM-CSF * Evaluable neuroblastoma outside bone and bone marrow * Existing major organ dysfunction \> Grade 2, with the exception of hearing loss, hematological status, kidney and liver function * Active life-threatening infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate during Naxitamab treatment | 101 weeks | Overall objective response rate (ORR) during the Naxitamab treatment period that will be centrally assessed according to the International Neuroblastoma Response Criteria (INRC) modified with 123I-MIBG criteria and following the use of 18F FDG-PET for MIBG non-avid lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events and serious adverse events | 101 weeks | Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0. |
| Duration of Response (DoR) | 101 weeks | Length of time from patient response to disease progression. |
| Complete Response Rate | 101 weeks | The complete response (CR) rate is defined as the fraction of patients experiencing a CR according to International Neuroblastoma Response Criteria (INRC) criteria during the treatment period. |
| Assessment of the maximum serum concentration (cmax) of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of the minimum serum concentration (cmin) of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of the clearance of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of the volume of distribution of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of the Area under the Curve (AUC) of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of the terminal half-life (t½) of naxitamab | Pre-naxitamab dose - 552 hours | Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics. |
| Assessment of anti-drug antibody (ADA) formation | Pre-naxitamab dose - 552 hours | ADA formation will be investigated following a multi-tiered approach: A screening confirmation-titration analysis plus a ligand binding assay to examine a potential neutralizing effect of anti-naxitamab antibodies. |
| Intravenous (IV) opioid use (cycle 1) | 6 hours | IV opioid use during cycle 1 defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab |
| Intravenous (IV) opioid use (all cycles) | 101 weeks | IV opioid use for each cycle during the trial defined as total dosage of IV morphine (or equivalent opioid) administered 2 hours before infusion until 4 hours after end of infusion of naxitamab |
| Hospitalization days (cycle 1) | 4 weeks | Number of hospitalization days related to naxitamab during cycle 1, defined as number of overnight stays. Hospitalizations required solely for protocol-specified assessments (e.g., PK sampling) or non-medical circumstances are excluded |
| Safety of patients with positive human anti-drug antibody (ADA) | 101 weeks | In patients with positive ADA at trial inclusion, safety will be evaluated by the incidence of AEs and SAEs graded according to CTCAE, version 4.0 |
| Number of infusions done in an outpatient setting | 101 weeks | Number of infusions done in an outpatient setting |
| Percentage of infusions done in an outpatient setting | 101 weeks | Percentage of infusions done in an outpatient setting |
| Incidence of adverse events and serious adverse events in ADA positive patients | 101 weeks | Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0 in ADA positive patients. |
| Progression Free Survival (PFS) | 5 years | PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first |
| Overall Survival | 5 years | The interval from the date of first dose of Naxitamab until the date of death due to any cause. |
| Happiness and activity levels | 39 days | Happiness and activity levels will be measured over time and assessed by caretaker |
Countries
Canada, Denmark, Germany, Hong Kong, India, Italy, Spain, United Kingdom, United States
Outcome results
None listed