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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GM-CSF + Naxitamab | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GM-CSF + Naxitamab | Biological | Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Humanized IgG1 monoclonal GD2 antibody |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Duration of Response (DoR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Riley Hospital for Children | Indianapolis | Indiana | 46202 | United States | ||
| Memorial Sloan Kettering Cancer Center |
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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.
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Length of time from patient response to disease progression.
| 101 weeks |
| 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 |
| 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 |
| 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 |
| Assessment of the clearance of naxitamab | Calculation of clearance of naxitamab will be calculated and summarized with descriptive statistics. | Pre-naxitamab dose - 552 hours |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Number of infusions done in an outpatient setting | Number of infusions done in an outpatient setting | 101 weeks |
| Percentage of infusions done in an outpatient setting | Percentage of infusions done in an outpatient setting | 101 weeks |
| 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 |
| 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 |
| Overall Survival | The interval from the date of first dose of Naxitamab until the date of death due to any cause. | 5 years |
| Happiness and activity levels | Happiness and activity levels will be measured over time and assessed by caretaker | 39 days |
| New York |
| New York |
| 10065 |
| United States |
| The Hospital for Sick Children | Toronto | M5G 1X8 | Canada |
| Rigshospitalet | Copenhagen | 2100 | Denmark |
| University Medical Center Hamburg-Eppendorf | Hamburg | Germany |
| Johannes Gutenberg-Universität | Mainz | Germany |
| University Hospital Regensburg | Regensburg | Germany |
| Hong Kong Children's Hospital | Hong Kong | Hong Kong |
| Queen Mary Hospital | Hong Kong | Hong Kong |
| Tata Memorial Centre | Mumbai | 400012 | India |
| Giannina Gaslini Hospital | Genoa | Genoa | 16147 | Italy |
| Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | Milan | 20133 | Italy |
| Ospedale Pediatrico Bambino Gesù | Rome | Italy |
| Hospital Sant Joan de Déu | Barcelona | 08950 | Spain |
| Hospital Infantil Universitario Niño Jesús | Madrid | 28009 | Spain |
| Hospital Universitario Virgen Del Rocío | Seville | Spain |
| Hospital Universitario y Politécnico La Fe | Valencia | 46026 | Spain |
| The Royal Glasgow Children's Hospital | Glasgow | G51 4TF | United Kingdom |
| Leeds General Infirmary | Leeds | LS1 3EX | United Kingdom |
| University Hospital Southampton | Southampton | SO16 6YD | United Kingdom |
| ID | Term |
|---|---|
| D009447 | Neuroblastoma |
| ID | Term |
|---|---|
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| D016178 | Granulocyte-Macrophage Colony-Stimulating Factor |
| C000718263 | naxitamab |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
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