Quadruple Immunotherapy for Neuroblastoma

Phase 2RecruitingNCT05754684

Hong Kong Children's Hospital29 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neuroblastoma Recurrent

Interventions

Natural killer cellBIOLOGICAL

Natural killer cells isolated from HLA-haploidentical relative donor

Dinutuximab betaDRUG

Dinutuximab beta iv for 5 days

Interleukin-2DRUG

Interleukin-2 sc alternate day for 6 doses

Eligibility

Sex: ALLMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Hong Kong Children's Hospital

Hong Kong, Hong Kong

RECRUITING

Outcomes

Primary Outcomes

Proportion of patients who have objective response in the tumor

Objective response = complete response + partial response + minor response + stable disease

Time frame: 1-2 months

Secondary Outcomes

Overall survival at 1 year

From the date of treatment start until the date of death from any cause, assessed up to 1 year

Time frame: 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

Time frame: up to 1 year

Proportion of patients who have tumor relapse

relapse = reappearance of tumor after complete response

Time frame: 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)

Time frame: 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

Time frame: up to 1 year

Central Contacts

Daniel Cheuk

CONTACT

852-35136049 cheukkld@gmail.com

Data from ClinicalTrials.gov

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