Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate for Neuroblastoma

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Children's Healthcare of Atlanta, Atlanta, GA
Neuroblastoma+2 More
Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate - CombinationProduct
Eligibility
< 18
All Sexes
What conditions do you have?
Select

Study Summary

High risk neuroblastoma is an aggressive and often lethal pediatric solid tumor. Survival remains less than 50% and those patients who do survive suffer many treatment-related acute and chronic toxicities. Chemoimmunotherapy using a combination of an anti-GD2 monoclonal antibody (dinutuximab) and different chemotherapy agents in the relapsed/refractory (r/r) neuroblastoma population, has demonstrated the most robust response rates to date, shifting the clinical practice to administer chemoimmunotherapy as a standard treatment for patients with r/r neuroblastoma. The goal of this study is to improve upon GD2 chemoimmunotherapy regimens for neuroblastoma by delivering standard drugs like temozolomide, irinotecan, and dinutuximab in combination with a novel cell-based immunotherapy called gamma delta (γδ) T cells in addition to zoledronate that enhances γδ T cell activation and potency. γδ T cells are an innovative approach to cell therapy for neuroblastoma as they are major histocompatibility complex (MHC) independent and directly cytotoxic to tumor cells without the need for engineering them to recognize the tumor. The study team has developed a Good Manufacturing Practice (GMP)-compliant manufacturing strategy to expand safe γδ T cells from healthy donors for this trial. This is a Phase 1 study to determine the safety, recommended phase 2 dose, and preliminary efficacy of allogeneic (third party), ex vivo expanded γδ T cells in combination with dinutuximab, temozolomide, irinotecan and zoledronate in children with refractory, relapsed, or progressive neuroblastoma.

Eligible Conditions

  • Neuroblastoma
  • Refractory Neuroblastoma
  • Relapsed Neuroblastoma

Treatment Effectiveness

Study Objectives

1 Primary · 3 Secondary · Reporting Duration: From Day 1 of protocol therapy through 30 days following end of protocol therapy

21 Days
Maximum Tolerated Dose/Recommended Phase 2 Dose of gamma delta T cells
Day 30
Overall Response
Day 30
Describe Hematological Toxicities
Describe Non-Hematological Toxicities

Trial Safety

Trial Design

1 Treatment Group

Dose Escalation Phase I cohort
1 of 1
Experimental Treatment

24 Total Participants · 1 Treatment Group

Primary Treatment: Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate · No Placebo Group · Phase 1

Dose Escalation Phase I cohort
CombinationProduct
Experimental Group · 1 Intervention: Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate · Intervention Types: CombinationProduct

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: from day 1 of protocol therapy through 30 days following end of protocol therapy

Trial Background

Prof. Kelly Goldsmith, Associate Professor
Principal Investigator
Emory University
Closest Location: Children's Healthcare of Atlanta · Atlanta, GA
Photo of Atlanta  1Photo of Atlanta  2Photo of Atlanta  3
2006First Recorded Clinical Trial
9 TrialsResearching Neuroblastoma
203 CompletedClinical Trials

Eligibility Criteria

Age < 18 · All Participants · 10 Total Inclusion Criteria

Mark “yes” if the following statements are true for you:
Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
You have recurrent/progressive disease after the diagnosis of high risk neuroblastoma at any time prior to study registration - regardless of response to frontline therapy.
You are 12 months of age or older.
You have a best overall response of no response/stable disease since diagnosis of high risk neuroblastoma AND after at least 4 courses of high risk neuroblastoma induction therapy.

About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 9th, 2021

Last Reviewed: August 12th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.