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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03363373

Studienbeginn:
April 2018

Letztes Update:
07.03.2023

Wirkstoff:
GM-CSF + Naxitamab

Indikation (Clinical Trials):
Neuroblastoma

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 2

Sponsor:
Y-mAbs Therapeutics

Collaborator:
-

Kontakt

Studienlocations
(3 von 24)

University Medical Center Hamburg-Eppendorf
Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Johannes Gutenberg-Universität
Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
University Hospital Regensburg
Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
University of Florida
32611 Gainesville
United StatesZurückgezogen» Google-Maps
University of Chicago
60637 Chicago
United StatesZurückgezogen» Google-Maps
Riley Hospital for Children
46202 Indianapolis
United StatesAktiv, nicht rekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesAktiv, nicht rekrutierend» Google-Maps
Nationwide Children's Hospital
43205 Columbus
United StatesZurückgezogen» Google-Maps
M.D. Anderson Cancer Center
77030 Houston
United StatesZurückgezogen» Google-Maps
The Hospital for Sick Children
M5G 1X8 Toronto
CanadaRekrutierend» Google-Maps
Hopital pour enfants de la Timone
13005 Marseille
FranceRekrutierend» Google-Maps
Queen Mary Hospital
Hong Kong
Hong KongAktiv, nicht rekrutierend» Google-Maps
Fondazione IRCCS Istituto Nazionale dei Tumori
20133 Milan
ItalyRekrutierend» Google-Maps
Hospital Infantil Universitario Niño Jesús
28009 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario Virgen Del Rocío
Sevilla
SpainNoch nicht rekrutierend» Google-Maps
Hospital Universitario y Politécnico La Fe
46026 Valencia
SpainRekrutierend» Google-Maps
The Royal Glasgow Children's Hospital
G51 4TF Glasgow
United KingdomRekrutierend» Google-Maps
Leeds General Infirmary
LS1 3EX Leeds
United KingdomRekrutierend» Google-Maps
University Hospital Southampton
SO16 6YD Southampton
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

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:

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 anti-drug antibody (ADA) formation (Time Frame - Pre-naxitamab dose - 552 hours):
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.

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 ADA 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.

20. Happiness and activity levels (Time Frame - 39 days):
Happiness and activity levels will be measured over time and assessed by caretaker

Geprüfte Regime

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

Quelle: ClinicalTrials.gov


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