Quadruple Immunotherapy for Neuroblastoma

Neuroblastoma Recurrent Clinical Trial

Official title:

Quadruple Immunotherapy for Paediatric Patients With Relapsed or Refractory Neuroblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754684
• Other study ID #: HKCH-REC-2021-007
• Status: Recruiting
• Phase: Phase 2
• Start date: January 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Hong Kong Children's Hospital
• Contact: Daniel Cheuk
• Phone: 852-35136049
• Email: cheukkld[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm clinical trial to evaluate the efficacy and safety of quadruple immunotherapy with natural killer (NK) cells, anti-GD2 antibody, cytokines (interleukin-2 (IL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF)) and retinoid X receptor gamma (RXRg) agonist spironolactone for paediatric patients with relapsed or refractory neuroblastoma.

Description:

Included patients will receive intravenous infusion of donor NK cells on day 0, and anti-GD2 antibody (dinutuximab) on day -6 to day -2. IL-2 will be given subcutaneously on day -1, day +1, day +3, day +5, day +7, and day +9. Subcutaneous injection of GM-CSF will be started on day 0, given daily till neutrophil count >1000/mm3. Spironolactone will be started orally on day -1, given three times daily till cessation of GM-CSF.

Alternative anti-GD2 antibody (Naxitamab) can be used instead of dinutuximab, to be given on day -5, day -3, day +1 and day +3.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

• relapsed or refractory neuroblastoma

• Adequate organ function: creatinine clearance =40 ml/min/1.73m2, total bilirubin =3 times upper limit of normal and ALT =500 IU/L, left ventricular shortening fraction =25%, and oxygen saturation =92% in room air

• Karnofsky or Lansky performance status score =50

• Has an appropriate HLA-haploidentical NK-cell donor available

Exclusion Criteria:

• Pregnant or lactating woman

• HIV infection

• Patients for whom conventional treatment is deemed more appropriate

• Patients who are unlikely to benefit, e.g., terminal malignancy with life expectancy <1 month

Related Conditions & MeSH terms

• Neuroblastoma
• Neuroblastoma Recurrent

Intervention

Biological:
• Natural killer cell
Natural killer cells isolated from HLA-haploidentical relative donor

Drug:
• Dinutuximab beta
Dinutuximab beta iv for 5 days
• Interleukin-2
Interleukin-2 sc alternate day for 6 doses
• Granulocyte-Macrophage Colony-Stimulating Factor
Granulocyte-macrophage colony-stimulating factor sc daily till ANC >2,000/mm3
• Spironolactone
Spironolactone po three time daily
• Naxitamab
Naxitamab iv for 4 days (as alternative for dinutuximab)

Locations

Country	Name	City	State
Hong Kong	Hong Kong Children's Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
Hong Kong Children's Hospital	The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who have objective response in the tumor	Objective response = complete response + partial response + minor response + stable disease	1-2 months
Secondary	Overall survival at 1 year	From the date of treatment start until the date of death from any cause, assessed up to 1 year	up to 1 year
Secondary	Progression-free survival	From date of treatment start until the date of first documented progression or the date of death from any cause, whichever comes first, assessed up to 1 year	up to 1 year
Secondary	Proportion of patients who have tumor relapse	relapse = reappearance of tumor after complete response	up to 1 year
Secondary	Number of patients who experience adverse events	Adverse events are graded according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5 (CTCAEv5)	up to 1 month
Secondary	Percentage of donor NK cells	Percentage of donor natural killer cells in the recipient's blood will be evaluated weekly from the date of NK cell infusion for 4 weeks, then every 2 weeks till donor NK cells are undetectable	up to 1 year