Quadruple Immunotherapy for Neuroblastoma

Quadruple Immunotherapy for Paediatric Patients With Relapsed or Refractory Neuroblastoma

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroblastoma Recurrent
• Intervention / Treatment: Biological: Natural killer cell; Drug: Dinutuximab beta; Drug: Interleukin-2; Drug: Granulocyte-Macrophage Colony-Stimulating Factor; Drug: Spironolactone; Drug: Naxitamab

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.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel Cheuk; Phone Number: 852-35136049; Email: cheukkld@gmail.com

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Hong Kong Children's Hospital
    • Contact: Daniel Cheuk; Phone Number: 851-35136049; Email: cheukkld@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; Quadruple immunotherapy

Biological: Natural killer cell; Natural killer cells isolated from HLA-haploidentical relative donor; Other Names: NK cell; Drug: Dinutuximab beta; Dinutuximab beta iv for 5 days; Other Names: Ch14.18; Drug: Interleukin-2; Interleukin-2 sc alternate day for 6 doses; Other Names: Aldesleukin; Drug: Granulocyte-Macrophage Colony-Stimulating Factor; Granulocyte-macrophage colony-stimulating factor sc daily till ANC >2,000/mm3; Other Names: Sargramostim; Drug: Spironolactone; Spironolactone po three time daily; Other Names: Aldactone; Drug: Naxitamab; Naxitamab iv for 4 days (as alternative for dinutuximab); Other Names: hu3F8

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hong Kong Children's Hospital
• Collaborators: The University of Hong Kong
• Investigators: Principal Investigator: Daniel Cheuk, Hong Kong Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): March 6, 2023

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Aldesleukin; Spironolactone; Sargramostim; Dinutuximab; Interleukin-2; Molgramostim
• Other Study ID Numbers: HKCH-REC-2021-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No