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

Neuroblastoma Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03363373
• Other study ID #: 201
• Status: Recruiting
• Phase: Phase 2
• Start date: April 3, 2018
• Est. completion date: April 2028

Study information

• Verified date: March 2023
• Source: Y-mAbs Therapeutics
• Contact: Joris Wilms
• Phone: +4570261414
• Email: clinicaltrials[@]ymabs.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: April 2028
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• GM-CSF + Naxitamab
Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto
Denmark	Rigshospitalet	København
France	Hopital pour enfants de la Timone	Marseille
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	Johannes Gutenberg-Universität	Mainz
Germany	University Hospital Regensburg	Regensburg
Hong Kong	Hong Kong Children's Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	Giannina Gaslini Hospital	Genoa
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan
Spain	Hospital Sant Joan de Déu	Barcelona
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Hospital Universitario Virgen Del Rocío	Sevilla
Spain	Hospital Universitario y Politécnico La Fe	Valencia
United Kingdom	The Royal Glasgow Children's Hospital	Glasgow
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	The Royal Marsden	London
United Kingdom	University Hospital Southampton	Southampton
United States	University of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Y-mAbs Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Hong Kong,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate during Naxitamab treatment	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.	101 weeks
Secondary	Incidence of adverse events and serious adverse events	Safety will be evaluated by the incidence of adverse events (AE) and serious adverse events (SAEs) graded according to CTCAE, version 4.0.	101 weeks
Secondary	Duration of Response (DoR)	Length of time from patient response to disease progression.	101 weeks
Secondary	Complete Response Rate	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.	101 weeks
Secondary	Assessment of the maximum serum concentration (cmax) of naxitamab	Calculation of maximum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of the minimum serum concentration (cmin) of naxitamab	Calculation of minimum serum concentration of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of the clearance of naxitamab	Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of the volume of distribution of naxitamab	Calculation of the volume of distribution of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of the Area under the Curve (AUC) of naxitamab	Calculation of the AUC of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of the terminal half-life (t½) of naxitamab	Calculation of the t½ of naxitamab will be calculated and summarized with descriptive statistics.	Pre-naxitamab dose - 552 hours
Secondary	Assessment of anti-drug antibody (ADA) formation	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.	Pre-naxitamab dose - 552 hours
Secondary	Intravenous (IV) opioid use (cycle 1)	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	6 hours
Secondary	Intravenous (IV) opioid use (all cycles)	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	101 weeks
Secondary	Hospitalization days (cycle 1)	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	4 weeks
Secondary	Safety of patients with positive human anti-drug antibody (ADA)	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	101 weeks
Secondary	Number of infusions done in an outpatient setting	Number of infusions done in an outpatient setting	101 weeks
Secondary	Percentage of infusions done in an outpatient setting	Percentage of infusions done in an outpatient setting	101 weeks
Secondary	Incidence of adverse events and serious adverse events in ADA positive patients	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.	101 weeks
Secondary	Progression Free Survival (PFS)	PFS, defined as the time from the first 1st infusion of naxitamab until progressive disease or death, whichever comes first	5 years
Secondary	Overall Survival	The interval from the date of first dose of Naxitamab until the date of death due to any cause.	5 years
Secondary	Happiness and activity levels	Happiness and activity levels will be measured over time and assessed by caretaker	39 days