Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed or Refractory Neuroblastoma — Aflac-NBL-2002  

Neuroblastoma Clinical Trial

Official title: A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells (IND # 28460) in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory, Relapsed, or Progressive Neuroblastoma

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

High risk neuroblastoma is an aggressive and lethal pediatric solid tumor. Survival remains less than 50% and those patients who do survive suffer many treatment-related acute and chronic toxicities, stressing a critical need for novel tumor-targeting therapies. γδ T cells are an innovative approach to cell therapy for neuroblastoma as they are MHC independent and directly cytolytic to tumor cells. We have developed a GMP-compliant manufacturing strategy to expand γδ T cells from normal donor and neuroblastoma patient apheresis products for this trial. This is a Phase 1 study to determine the safety, recommended phase 2 cell therapy dose, and preliminary efficacy of allogenic (third party) ex vivo expanded gamma delta (γδ) T cells in combination with dinutuximab, temozolomide, irinotecan and zoledronate in children with refractory, relapsed, or progressive neuroblastoma. The purpose of this study is to help doctors and scientists learn if γδ T cells will aid in clinical and disease response in this population and to determine the maximum tolerated dose (MTD). This is a single-site non-randomized clinical trial, that will take place at Children's Healthcare of Atlanta (CHOA) at Egleston. Third party γδ T cells will be prepared from healthy donors and expanded under GMP conditions at Expression Therapeutics, LLC. γδ T cells will be expanded, cryopreserved as numerous aliquots, and transported to The Children's Healthcare of Atlanta, Egleston Campus. At the appropriate time, an aliquot of γδ T cells appropriate for the size of the subject will be thawed and infused into the patient according to institutional protocol. Subjects will receive a single infusion of third party, ex vivo expanded, frozen then thawed γδ T cell product on Day 6 and then if they meet criteria for subsequent γδ T cell dose will receive a second dose on Day 13. The γδ T cell dose will be infused after the dinutuximab, temozolomide, irinotecan and zoledronate schedule is complete. There will be no intra-patient dose escalation. The entry dose level is Dose Level 1, with escalation up to Dose Level 3 following standard 3+3 rules for γδ T cell dose escalation design. If a subject does not want to enter into the clinical trial, they may choose an alternative therapy for r/r neuroblastoma that their physician deems appropriate. There will be no compensation for participation in this study. A minimum of 6 and a maximum of 24 patients with refractory, relapsed, or progressive neuroblastoma will be recruited through a variety of strategies, including: face to face encounters between participants and study staff during clinical encounters at Children's Healthcare of Atlanta, Institutional Review Board approved advertisement flyer, and potential subjects will be referred to the investigators for information about the potential benefits and side effects of the treatment regimen. An approved informed consent statement will be read and signed by the legal guardian, and an investigator. Written assent will be obtained from children ages 11 to 17, using an approved assent statement, along with use of the informed consent by their parent or guardian. Verbal assent will be obtained from children ages 6-10 years. Leftover blood samples collected may be stored for future research by the sponsor of this study. This research will advance scientific knowledge and clinical data in the neuroblastoma field and knowledge of γδ T cells. Cell therapy has been a promising treatment for neuroblastoma, so with this advancement in T cell therapy, we can potentially advance patient outcomes. ;

Related Conditions & MeSH terms

• Neuroblastoma
• Refractory Neuroblastoma
• Relapsed Neuroblastoma

• NCT number: NCT05400603
• Study type: Interventional
• Source: Emory University
• Contact: Kelly Goldsmith, MD
• Phone: (404) 727-2655
• Email: kgoldsm@emory.edu; mpactcto@choa.org
• Status: Recruiting
• Phase: Phase 1
• Start date: November 6, 2023
• Completion date: December 2025