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
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
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.
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.
Sequential
Ex Vivo Expanded Allogeneic γδ T Cells in Combination with Dinutuximab, Temozolomide, Irinotecan and Zoledronate
Combination productThe 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.
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
Describe Non-Hematological Toxicities
Proportion of patients with any Grade 3 or greater non-hematological toxicities on any course
Describe Hematological Toxicities
Proportion of patients with any Grade 3 or greater hematological toxicities on any course
Overall Response
Proportion of patients evaluable for response with a best overall response of CR/PR
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