Quadruple Immunotherapy for Neuroblastoma

Study Overview
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Brief Summary
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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.

Detailed Description
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Included patients will receive intravenous infusion of donor NK cells on day 0, and anti-GD2 antibody 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.

Official Title
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Quadruple Immunotherapy for Paediatric Patients With Relapsed or Refractory Neuroblastoma

Conditions
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Neuroblastoma Recurrent

Intervention / Treatment
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* Biological: Natural killer cell
* Drug: Dinutuximab beta
* Drug: Interleukin-2
* Drug: Granulocyte-Macrophage Colony-Stimulating Factor
* Drug: Spironolactone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Quadruple immunotherapy | Biological: Natural killer cell<br>* Natural killer cells isolated from HLA-haploidentical relative donor<br>* Other names: NK cell;Drug: Dinutuximab beta<br>* Dinutuximab beta iv for 5 days<br>* Other names: Ch14.18;Drug: Interleukin-2<br>* Interleukin-2 sc alternate day for 6 doses<br>* Other names: Aldesleukin;Drug: Granulocyte-Macrophage Colony-Stimulating Factor<br>* Granulocyte-macrophage colony-stimulating factor sc daily till ANC >2,000/mm3<br>* Other names: Sargramostim;Drug: Spironolactone<br>* Spironolactone po three time daily<br>* Other names: Aldactone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have objective response in the tumor | Objective response = complete response + partial response + minor response + stable disease | 1-2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Proportion of patients who have tumor relapse | relapse = reappearance of tumor after complete response | up to 1 year | 
| 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 | 
| 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 |