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Trial record 2 of 531 for:    "Neuroblastoma"

Naxitamab for Neuroblastoma With Osteomedullary Disease

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ClinicalTrials.gov Identifier: NCT03363373
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
Y-mAbs Therapeutics

Brief Summary:

Children and adults diagnosed with high risk neuroblastoma and refractory osteomedullary disease will be treated for up to 93 weeks with naxitamab and granulocyte-macrophage colony stimulating factor (GM-CSF). Participants 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 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.

The first 5 cycles are repeated every 4 weeks up to week 21 and after that the frequency decreases to every 8 weeks through a total of 93 weeks. End of treatment will take place around 8 weeks after the last cycle and thereafter long-term follow-up will continue.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Participants will receive up to 15 cycles of GM-CSF and Naxitamab for a total of 93 weeks. Safety and efficacy will be investigated with short-term follow-up at 8 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 : December 2020
Estimated Study Completion Date : December 2023

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. After 15 cycles at week 101 participants 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. Progression Free Survival (PFS) [ Time Frame: 101 weeks ]
    PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first

  5. Overall Survival [ Time Frame: 101 weeks ]
    The interval from the date of first dose of Naxitamab until the date of death due to any cause.

  6. Assessment of the maximum serum concentration (cmax) of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.

  7. Assessment of the minimum serum concentration (cmin) of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.

  8. Assessment of the clearance of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics.

  9. Assessment of the volume of distribution of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics.

  10. Assessment of the Area under the Curve (AUC) of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics.

  11. Assessment of the terminal half-life (t½) of naxitamab [ Time Frame: Pre-naxitamab dose - 264 hours ]
    Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics.

  12. Assessment of human anti-human antibody (HAHA) formation [ Time Frame: Pre-naxitamab dose - 264 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.

  13. 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

  14. Intravenous (IV) opioid use (all cycles) [ Time Frame: 93 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

  15. 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

  16. Safety of patients with positive human anti-human antibody (HAHA) [ 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



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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
Contact: Joris Wilms +4570261414 clinicaltrials@ymabs.com

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32611
United States, Indiana
Riley Hospital for Children Recruiting
Indianapolis, Indiana, United States, 46202
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
United States, Texas
M.D. Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Canada
The Hospital for Sick Children Not yet recruiting
Toronto, Canada, M5G 1X8
Denmark
Rigshospitalet Recruiting
København, Denmark, 2100
Hong Kong
Queen Mary Hospital Not yet recruiting
Hong Kong, Hong Kong
Spain
Hospital Sant Joan de Déu Recruiting
Barcelona, Spain, 08950
Hospital Infantil Universitario Niño Jesús Not yet recruiting
Madrid, Spain, 28009
Hospital Universitario y Politécnico La Fe Not yet recruiting
Valencia, Spain, 46026
United Kingdom
The Royal Glasgow Children's Hospital Not yet recruiting
Glasgow, United Kingdom, G51 4TF
Leeds General Infirmary Not yet recruiting
Leeds, United Kingdom, LS1 3EX
The Royal Marsden Not yet recruiting
London, United Kingdom, SW3 6JJ
University Hospital Southampton Not yet recruiting
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Y-mAbs Therapeutics
Investigators
Study Director: Steen Lisby, MD Chief Medical Officer

Responsible Party: Y-mAbs Therapeutics
ClinicalTrials.gov Identifier: NCT03363373     History of Changes
Other Study ID Numbers: 201
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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:
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
Antibodies
Immunologic Factors
Physiological Effects of Drugs