Quadruple Immunotherapy for Neuroblastoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention Quadruple immunotherapy |
Biological: Natural killer cell
Natural killer cells isolated from HLA-haploidentical relative donor
Other Names:
Drug: Dinutuximab beta
Dinutuximab beta iv for 5 days
Other Names:
Drug: Interleukin-2
Interleukin-2 sc alternate day for 6 doses
Other Names:
Drug: Granulocyte-Macrophage Colony-Stimulating Factor
Granulocyte-macrophage colony-stimulating factor sc daily till ANC >2,000/mm3
Other Names:
Drug: Spironolactone
Spironolactone po three time daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients who have objective response in the tumor [1-2 months]
Objective response = complete response + partial response + minor response + stable disease
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hong Kong Children's Hospital | Hong Kong | Hong Kong |
Sponsors and Collaborators
- Hong Kong Children's Hospital
- The University of Hong Kong
Investigators
- Principal Investigator: Daniel Cheuk, Hong Kong Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HKCH-REC-2021-007