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

NCT05400603 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY000031232025P010043
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Refractory Osteosarcoma; Neuroblastoma; Refractory Neuroblastoma; Relapsed Neuroblastoma; Relapsed Osteosarcoma

Keywords

Gamma Delta T Cells; Dinutuximab; Temozolomide; Zoledronate; Irinotecan; GD2; chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose/Recommended Phase 2 Dose of gamma delta T cells

  The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for adverse event (AE) reporting. The MTD/RP2D is defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity course

  21 Days

Secondary Outcomes (3)

• Describe Non-Hematological Toxicities

  all toxicities from enrollment through 30 days following end of protocol therapy

• Describe Hematological Toxicities

  all toxicities from enrollment through 30 days following end of protocol therapy

• Overall Response

  From Day 1 of protocol therapy through 30 days following end of protocol therapy

Study Arms (1)

Dose Escalation Phase I cohort

EXPERIMENTAL

Subjects are assigned a cell therapy dose level at registration. Entry dose is Level 1, with escalation to Level 3 using a 3+3 design. If no progression, up to 4 courses may be given. Each course includes two γδ T cell infusions, one week apart. Toxicity for dose escalation and MTD will be assessed in Course 1. Disease response will be evaluated after Courses 2 and 4. Dinutuximab (17.5 mg/m²), temozolomide (100 mg/m²), irinotecan (50 mg/m²), and zoledronate (0.0125 mg/kg) are consistent across dose levels. Same γδ T cell donor will be used for both infusions per course. Due to stock supply, this may not always be possible. In each cohort, the first two subjects are staggered; the second is enrolled only after the first completes the DLT observation (≥21 days).

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

Interventions

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

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.

Dose Escalation Phase I cohort

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be ≥ 12 months of age at the time of enrollment in the study.
• Diagnosis: Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. (Bone marrow samples with positive catecholamines are acceptable as confirmation of neuroblastoma) OR histological confirmation of osteosarcoma at diagnosis
• Response to prior therapy:
• High-risk neuroblastoma with refractory, relapsed or progressive disease, defined as:
• First or greater relapse of neuroblastoma following completion of aggressive multi- drug frontline therapy.
• First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy.
• Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) after at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
• Note that this excludes patients initially considered low or intermediate-risk neuroblastoma that progressed to high-risk disease but the patient has not progressed after the diagnosis of high-risk neuroblastoma.
• Relapsed or refractory osteosarcoma that is not responsive to standard treatment
• Disease Status
• Patients must have measurable or evaluable disease per revised INRC for subjects with neuroblastoma or measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with Osteosarcoma
• Performance Level:Patients must have a Lansky (≤16 years) or Karnofsky (\>16 years) score of ≥50
• Prior Therapy
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study registration.
• Prior dinutuximab therapy is allowed regardless of prior response or progression on dinutuximab

You may not qualify if:

• Prior T cell therapy
• Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this study.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Patients with known active Central Nervous System (CNS) disease (excluding skull disease with intracranial extension). Patients with a history of CNS disease are required to have a brain CT and/ or MRI at study registration.
• Patients with prior allogeneic stem cell transplant
• Patients who are on hemodialysis
• Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.
• Patients with disease of any major organ system that would compromise their ability to withstand therapy.
• Patients who have had to permanently discontinue Dinutuximab due to toxicity
• Patients with serious, uncontrolled cardiac arrhythmias
• Patients with a history of myocarditis
• Patients who have received any live vaccines within 30 days before enrollment

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma

Interventions

dinutuximab; Temozolomide; Irinotecan; Zoledronic Acid

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Diphosphonates; Organophosphonates; Organophosphorus Compounds

Study Officials

• Kelly Goldsmith, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Goldsmith, MD

CONTACT

(404) 727-2655; kgoldsm@emory.edu; mpactcto@choa.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: June 1, 2022
• Study Start: November 6, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be come available once approved by the study Data Safety Monitoring Committee and made public through manuscript. No end date.
• Access Criteria: With the scientific public and community through presentation of results at national/international meetings and through manuscript submissions. All trial endpoints in the clinical study by peer reviewed manuscript submission, national meeting abstract submission/presentations.

Locations

US (1)