Quadruple Immunotherapy for Neuroblastoma

Hong Kong Children's Hospital

Status and phase: Enrolling; Phase 2

Conditions: Neuroblastoma Recurrent

Treatments: Drug: Granulocyte-Macrophage Colony-Stimulating Factor; Drug: Interleukin-2; Drug: Dinutuximab beta; Drug: Naxitamab; Biological: Natural killer cell; Drug: Spironolactone

Study type: Interventional

Funder types: Other

Identifiers

NCT05754684

HKCH-REC-2021-007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Intervention

Experimental group

Description:

Quadruple immunotherapy

Treatment:

Drug: Spironolactone

Biological: Natural killer cell

Drug: Naxitamab

Drug: Interleukin-2

Drug: Dinutuximab beta

Drug: Granulocyte-Macrophage Colony-Stimulating Factor