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NCT Number: NCT03363373

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Neuroblastoma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral

Age range

1 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Hospital for Sick Children, Toronto, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

GM-CSF + Naxitamab

Biological

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody

Primary outcomes

  1. Response rate during Naxitamab treatment

    Time frame: 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 outcomes

  1. Incidence of adverse events and serious adverse events

    Time frame: 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.

  2. Duration of Response (DoR)

    Time frame: 101 weeks

    Length of time from patient response to disease progression.

  3. Complete Response Rate

    Time frame: 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.

  4. Assessment of the maximum serum concentration (cmax) of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.

  5. Assessment of the minimum serum concentration (cmin) of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.

  6. Assessment of the clearance of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics.

  7. Assessment of the volume of distribution of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics.

  8. Assessment of the Area under the Curve (AUC) of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics.

  9. Assessment of the terminal half-life (t½) of naxitamab

    Time frame: Pre-naxitamab dose - 552 hours

    Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics.

  10. Assessment of anti-drug antibody (ADA) formation

    Time frame: 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.

  11. Intravenous (IV) opioid use (cycle 1)

    Time frame: 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

  12. Intravenous (IV) opioid use (all cycles)

    Time frame: 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

  13. Hospitalization days (cycle 1)

    Time frame: 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

  14. Safety of patients with positive human anti-drug antibody (ADA)

    Time frame: 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

  15. Number of infusions done in an outpatient setting

    Time frame: 101 weeks

    Number of infusions done in an outpatient setting

  16. Percentage of infusions done in an outpatient setting

    Time frame: 101 weeks

    Percentage of infusions done in an outpatient setting

  17. Incidence of adverse events and serious adverse events in ADA positive patients

    Time frame: 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.

  18. Progression Free Survival (PFS)

    Time frame: 5 years

    PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first

  19. Overall Survival

    Time frame: 5 years

    The interval from the date of first dose of Naxitamab until the date of death due to any cause.

  20. Happiness and activity levels

    Time frame: 39 days

    Happiness and activity levels will be measured over time and assessed by caretaker

Sponsors and collaborators

Lead sponsor

Y-mAbs Therapeutics

Industry

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2026
Study completion
2028
First posted
Dec 6, 2017
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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