Description:
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
Title
- Brief Title: Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow
- Official Title: A Pivotal Phase 2 Trial of Antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow
Clinical Trial IDs
- ORG STUDY ID:
201
- NCT ID:
NCT03363373
Conditions
Interventions
Drug | Synonyms | Arms |
---|
GM-CSF + Naxitamab | | GM-CSF + Naxitamab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
GM-CSF + Naxitamab | Experimental | Each investigational cycle is started with 5 days of 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 until CR or PR 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. After end of treatment patients will enter a long-term follow up for up to 3 years after end of treatment visit. | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 1 Year |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Response rate during Naxitamab treatment |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | 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 Outcome Measures
Measure: | Incidence of adverse events and serious adverse events |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0. |
Measure: | Duration of Response (DoR) |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | Length of time from patient response to disease progression. |
Measure: | Complete Response Rate |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Assessment of the maximum serum concentration (cmax) of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of the minimum serum concentration (cmin) of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of the clearance of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of the volume of distribution of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of the Area under the Curve (AUC) of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of the terminal half-life (t½) of naxitamab |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics. |
Measure: | Assessment of anti-drug antibody (ADA) formation |
Time Frame: | Pre-naxitamab dose - 552 hours |
Safety Issue: | |
Description: | 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. |
Measure: | Intravenous (IV) opioid use (cycle 1) |
Time Frame: | 6 hours |
Safety Issue: | |
Description: | 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 |
Measure: | Intravenous (IV) opioid use (all cycles) |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | 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 |
Measure: | Hospitalization days (cycle 1) |
Time Frame: | 4 weeks |
Safety Issue: | |
Description: | 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 |
Measure: | Safety of patients with positive human anti-drug antibody (ADA) |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | 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 |
Measure: | Number of infusions done in an outpatient setting |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | Number of infusions done in an outpatient setting |
Measure: | Percentage of infusions done in an outpatient setting |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | Percentage of infusions done in an outpatient setting |
Measure: | Incidence of adverse events and serious adverse events in ADA positive patients |
Time Frame: | 101 weeks |
Safety Issue: | |
Description: | 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. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 5 years |
Safety Issue: | |
Description: | PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first |
Measure: | Overall Survival |
Time Frame: | 5 years |
Safety Issue: | |
Description: | The interval from the date of first dose of Naxitamab until the date of death due to any cause. |
Measure: | Happiness and activity levels |
Time Frame: | 39 days |
Safety Issue: | |
Description: | Happiness and activity levels will be measured over time and assessed by caretaker |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Y-mAbs Therapeutics |
Trial Keywords
- Antibody, Neuroblastoma, Pediatric, Adult
Last Updated
July 14, 2021