Clinical trial NCT03363373: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: Antibody, Neuroblastoma, Pediatric, Adult
Lead sponsor: Y-mAbs Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-12-06
Enrollment: 122
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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

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.

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

Primary outcomes:
measure: Response rate during Naxitamab treatment
timeFrame: 101 weeks
Secondary outcomes:
measure: Incidence of adverse events and serious adverse events
timeFrame: 101 weeks
measure: Duration of Response (DoR)
timeFrame: 101 weeks
measure: Complete Response Rate
timeFrame: 101 weeks
measure: Assessment of the maximum serum concentration (cmax) of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of the minimum serum concentration (cmin) of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of the clearance of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of the volume of distribution of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of the Area under the Curve (AUC) of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of the terminal half-life (t½) of naxitamab
timeFrame: Pre-naxitamab dose - 552 hours
measure: Assessment of anti-drug antibody (ADA) formation
timeFrame: Pre-naxitamab dose - 552 hours
measure: Intravenous (IV) opioid use (cycle 1)
timeFrame: 6 hours
measure: Intravenous (IV) opioid use (all cycles)
timeFrame: 101 weeks
measure: Hospitalization days (cycle 1)
timeFrame: 4 weeks
measure: Safety of patients with positive human anti-drug antibody (ADA)
timeFrame: 101 weeks
measure: Number of infusions done in an outpatient setting
timeFrame: 101 weeks
measure: Percentage of infusions done in an outpatient setting
timeFrame: 101 weeks
measure: Incidence of adverse events and serious adverse events in ADA positive patients
timeFrame: 101 weeks
measure: Progression Free Survival (PFS)
timeFrame: 5 years
measure: Overall Survival
timeFrame: 5 years
measure: Happiness and activity levels
timeFrame: 39 days
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: The Hospital for Sick Children
city: København
country: Denmark
facility: Rigshospitalet
city: Marseille
country: France
facility: Hopital pour enfants de la Timone
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Genoa
country: Italy
facility: Giannina Gaslini Hospital
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Glasgow
country: United Kingdom
facility: The Royal Glasgow Children's Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: The Royal Marsden
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
References: