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

Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06013618
• Other study ID #: 3F8-RWS
• Status: Recruiting
• Phase: Phase 2
• Start date: June 19, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2023
• Source: Sun Yat-sen University
• Contact: Yizhuo Zhang, MD
• Phone: 0087342460
• Email: zhangyzh[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• Naxitamab monotherapy
Naxitamab is administered on days 1, 3, and 5
• 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.
• 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.
• 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.
• Naxitamab in combination therapy
Naxitamab 2.25mg/kg IV will be administered on Days 2, 4, 8 and 10.
• GM-CSF with combination regimen
GM-CSF 250 mcg/m2/day will be administered subcutaneously on Days 6-10.
• Sintilimab
Sintilimab was administerd with 3mg/kg (max 200mg) on day 11 every 3 weeks.

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Hainan General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	The proportion of patients who achieved CR or PR	from start of naxitamab treatment to 1.5 years after EOT
Secondary	DCR	The proportion of patients who achieved CR or PR or SD	from start of naxitamab treatment to 1.5 years after EOT
Secondary	EFS	The time from from start of naxitamab treatment to disease progression, recurrence	from start of naxitamab treatment to 1.5 years after EOT
Secondary	OS	The time from from start of naxitamab treatment to death or loss of follow-up	from start of naxitamab treatment to 1.5 years after EOT