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Clinical Analysis of Naxitamab (hu3F8) in the Treatment of Pediatric High Risk or Refractory/ Relapsed Neuroblastoma

Registration Number
NCT06013618
Lead Sponsor
Sun Yat-sen University
Brief Summary

This is an prospective study to evaluate the safety and efficacy of naxitamab monotherapy or combined with chemotherapy or combined with chemotherapy and checkpoint inhibitor in the treatment of pediatric high-risk and refractory/relapsed neuroblastoma in Sun Yat-sen University Cancer Center.

Detailed Description

Patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation received axitamab and GM-CSF. Patients with high-risk neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory) received naxitamab and GM-CSF in combination with irinotecan and temozolomide or naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria

1)Confirmed diagnosis of high-risk NB 2)1 year of age or above 3)Patient or parent/guardian must provide written informed consent to participate 4)If patient is sexually active, the patient agrees to use effective contraception 5)Confirmed negative urine pregnancy test for sexually active female of child-bearing potential (post-menarche)

Exclusion Criteria
  1. Significant organ toxicity

  2. Known or suspected allergy or hypersensitivity to anti-GD2 antibodies or to GM-CSF or its s components.

  3. Patient is pregnant, planning to become pregnant (while being treated with naxitamab) or is currently breastfeeding

  4. Patient will undergo treatment with another investigational drug, whilst being treated with naxitamab or has received another investigational drug within the 4 weeks prior to commencing treatment with naxitamab

  5. Patient is either eligible and able to participate in or is currently participating in an active interventional Y-mAbs sponsored clinical trial with naxitamab within the indication applied for

  6. Patient is unable to comply with the naxitamab treatment or has a medical condition that would potentially increase the severity of the toxicities experienced from naxitamab treatment at the discretion of the treating physician

  7. Left ventricular ejection fraction of <50% by echocardiography OR other clinically relevant cardiac disorders at the discretion of the investigator

  8. Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated

    Applicable for treatment with naxitamab in combination with GM-CSF only:

  9. Patient has active progression of the NB disease

  10. Patient has active NB disease at primary site or soft-tissue metastasis

  11. Patient has known CNS metastases when initiating naxitamab treatment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
naxitamab and GM-CSF in combination with irinotecan and temozolomideNaxitamab in combination therapySuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomideTemozolomideSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibodyGM-CSF with combination regimenSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF onlyNaxitamab monotherapySuitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs.
naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibodySintilimabSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF onlyGM-CSFSuitable for patients with high risk neuroblastoma who obtain CR after chemotherapy combined with surgery, radiotherapy and/or hematopoietic stem cell transplantation. The treatment cycle is repeated every 4 weeks for a total of 5 courses, and discontinuation of nasetuzumab and GM-CSF should be considered if disease progression or unacceptable toxicity occurs.
naxitamab and GM-CSF in combination with irinotecan and temozolomideGM-CSF with combination regimenSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibodyNaxitamab in combination therapySuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomideIrinotecanSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibodyIrinotecanSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibodyTemozolomideSuitable for high-risk group neuroblastoma treated by chemotherapy combined with surgery, radiotherapy and or hematopoietic stem cell transplantation patients with tumor residual or progression during treatment (refractory); Patients who relapse after initial treatment. Repeat every 3 weeks until tumor progression, patient withdrawal, or toxicity becomes intolerable, up to 8 procedures.
Primary Outcome Measures
NameTimeMethod
ORRfrom start of naxitamab treatment to 1.5 years after EOT

The proportion of patients who achieved CR or PR

Secondary Outcome Measures
NameTimeMethod
OSfrom start of naxitamab treatment to 1.5 years after EOT

The time from from start of naxitamab treatment to death or loss of follow-up

DCRfrom start of naxitamab treatment to 1.5 years after EOT

The proportion of patients who achieved CR or PR or SD

EFSfrom start of naxitamab treatment to 1.5 years after EOT

The time from from start of naxitamab treatment to disease progression, recurrence

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center

🇨🇳

Guangzhou, Guangdong, China

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