NCT05400603

Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed /Refractory Neuroblastoma or Refractory/ Relapsed Osteosarcoma

A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory/ Relapsed, or Progressive Neuroblastoma or Refractory/ Relapsed Osteosarcoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 12 Months
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory/ relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate

Detailed description

High-risk neuroblastoma and metastatic osteosarcoma are aggressive and lethal pediatric solid tumors. 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 and osteosarcoma as they are MHC-independent and directly cytolytic to tumor cells. The team has 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 or osteosarcoma. 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). 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 the 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. A minimum of 6 and a maximum of 24 patients with refractory, relapsed, or progressive neuroblastoma or osteosarcoma will be recruited through various strategies, including face-to-face encounters between participants and study staff during clinical encounters at CHOA. 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 solid tumor field and knowledge of γδ T cells. Cell therapy has been a promising treatment for solid tumors, so with this advancement in T-cell therapy, the team can potentially advance patient outcomes.

Conditions

• Neuroblastoma
• Refractory Neuroblastoma
• Relapsed Neuroblastoma
• Relapsed Osteosarcoma
• Refractory Osteosarcoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate	The cell dose will be based on the subject's body weight. Subjects will receive a single infusion of third party, ex vivo expanded, frozen then thawed γδ T cell product at a dose of 3 x 106 cells/kg on Day 6 and then if they meet criteria for subsequent γδ T cell dose will receive a second dose of 3 x 106 cells/kg on Day 13. The dose will be escalated to 1 x 10\^7 and then 3 x 10\^7 cells/kg. In absence of any dose limiting toxicity, 3 x 10\^7 cells/kg will be accepted as the maximal dose. Dinutuximab (17.5 mg/m2), temozolomide (100 mg/m2),irinotecan (50 mg/m2) and zoledronic acid (0.0125 mg/kg/dose) will be consistent across all dose levels. Max γδ T cell dose will not exceed Level 3 dosing at 50 kg: 1.5×10⁹ total γδ T cells.

Timeline

• Start date: 2023-11-06
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2022-06-01
• Last updated: 2025-12-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study