Clinical Trials /

Naxitamab for High-Risk Neuroblastoma Patients With Primary Refractory Disease or Incomplete Response to Salvage Treatment in Bone and/or Bone Marrow

NCT03363373

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

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

  • Neuroblastoma

Interventions

DrugSynonymsArms
GM-CSF + NaxitamabGM-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 93 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 93 weeks following the first Naxitamab
      administration and remain in the trial for 101 weeks. 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

NameTypeDescriptionInterventions
GM-CSF + NaxitamabExperimentalEach 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.
  • GM-CSF + Naxitamab

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:Progression Free Survival (PFS)
Time Frame:101 weeks
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:101 weeks
Safety Issue:
Description:The interval from the date of first dose of Naxitamab until the date of death due to any cause.
Measure:Assessment of the maximum serum concentration (cmax) of naxitamab
Time Frame:Pre-naxitamab dose - 264 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 - 264 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 - 264 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 - 264 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 - 264 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 - 264 hours
Safety Issue:
Description:Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics.
Measure:Assessment of human anti-human antibody (HAHA) formation
Time Frame:Pre-naxitamab dose - 264 hours
Safety Issue:
Description:HAHA 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:93 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-human antibody (HAHA)
Time Frame:101 weeks
Safety Issue:
Description:In patients with positive HAHA 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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Y-mAbs Therapeutics

Trial Keywords

  • Antibody, Neuroblastoma, Pediatric, Adult

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