Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03363373
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : January 9, 2020
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

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


Condition or disease Intervention/treatment Phase
Neuroblastoma Biological: GM-CSF + Naxitamab Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 3, 2018
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: GM-CSF + Naxitamab
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.
Biological: GM-CSF + Naxitamab
Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody




Primary Outcome Measures :
  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 Outcome Measures :
  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 human anti-human antibody (HAHA) formation [ Time Frame: Pre-naxitamab dose - 552 hours ]
    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.

  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 HAHA 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363373


Contacts
Layout table for location contacts
Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com

Locations
Show Show 17 study locations
Sponsors and Collaborators
Y-mAbs Therapeutics
Investigators
Layout table for investigator information
Study Director: Steen Lisby, MD Chief Medical Officer
Layout table for additonal information
Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT03363373    
Other Study ID Numbers: 201
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: January 9, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Y-mAbs Therapeutics:
Antibody, Neuroblastoma, Pediatric, Adult
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue