Neuroblastoma Recurrent
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGSpironolactone
Spironolactone po three time daily
BIOLOGICALNatural killer cell
Natural killer cells isolated from HLA-haploidentical relative donor
DRUGDinutuximab beta
Dinutuximab beta iv for 5 days
DRUGInterleukin-2
Interleukin-2 sc alternate day for 6 doses
Granulocyte-macrophage colony-stimulating factor sc daily till ANC \>2,000/mm3
DRUGNaxitamab
Naxitamab iv for 4 days (as alternative for dinutuximab)
Sponsors
The University of Hong Kong
Hong Kong Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who have objective response in the tumor | 1-2 months | Objective response = complete response + partial response + minor response + stable disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival at 1 year | up to 1 year | From the date of treatment start until the date of death from any cause, assessed up to 1 year |
| Progression-free survival | up to 1 year | 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 |
| Proportion of patients who have tumor relapse | up to 1 year | relapse = reappearance of tumor after complete response |
| Number of patients who experience adverse events | up to 1 month | Adverse events are graded according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5 (CTCAEv5) |
| Percentage of donor NK cells | up to 1 year | 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 |
Countries
Hong Kong
Contacts
Primary ContactDaniel Cheuk
Outcome results
None listed