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

NCT ID: NCT06013618

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-19
• Study Completion Date: 2027-12-31

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

naxitamab and GM-CSF only

Suitable 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.

Group Type: OTHER

Naxitamab monotherapy

Intervention Type: DRUG

Naxitamab is administered on days 1, 3, and 5

GM-CSF

Intervention Type: DRUG

Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5.

naxitamab and GM-CSF in combination with irinotecan and temozolomide

Suitable 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.

Group Type: OTHER

Irinotecan

Intervention Type: DRUG

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Temozolomide

Intervention Type: DRUG

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Naxitamab in combination therapy

Intervention Type: DRUG

Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.

GM-CSF with combination regimen

Intervention Type: DRUG

GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.

naxitamab and GM-CSF in combination with irinotecan and temozolomide and PD-1 antibody

Suitable 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.

Group Type: OTHER

Irinotecan

Intervention Type: DRUG

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Temozolomide

Intervention Type: DRUG

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Naxitamab in combination therapy

Intervention Type: DRUG

Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.

GM-CSF with combination regimen

Intervention Type: DRUG

GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.

Sintilimab

Intervention Type: DRUG

Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.

Interventions

Naxitamab monotherapy

Naxitamab is administered on days 1, 3, and 5

Intervention Type: DRUG

GM-CSF

Each treatment cycle is 28 days and is started with five days (days -4 to 0) of GM-CSF administered at 250 mcg/m2/day in advance of the start of naxitamab infusion. GM-CSF is thereafter administered at 500 mcg/m2/day on days 1 to 5.

Intervention Type: DRUG

Irinotecan

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Intervention Type: DRUG

Temozolomide

Each HITS treatment cycle is 21 days. Irinotecan intravenously (IV) at 50 mg/m2/day will be administered from Day 1-5 concurrently with temozolomide orally at 150 mg/m2/day or 100 mg/m2/day.

Intervention Type: DRUG

Naxitamab in combination therapy

Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.

Intervention Type: DRUG

GM-CSF with combination regimen

GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.

Intervention Type: DRUG

Sintilimab

Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.

Intervention Type: DRUG

Other Intervention Names

hu3F8; Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor; DNA topoisomerase I inhibitor; Temozolomide for Injection; hu3F8; Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor; PD-1 antibody

Eligibility Criteria

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

• Minimum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hainan General Hospital

OTHER

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yizhuo Zhang

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yizhuo Zhang

Role: STUDY_CHAIR

SunYat Sen University Cancer Center

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yizhuo Zhang, MD

Role: CONTACT

zhangyzh@sysucc.org.cn

0087342460

Juan Wang

Role: CONTACT

wangjuan@sysucc.org.cn

008687342660

Facility Contacts

Yi-Zhuo Zhang, MD

Role: primary

zhangyzh@sysucc.org.cn

87342460

Other Identifiers

3F8-RWS

Identifier Type: -

Identifier Source: org_study_id