Donor Immune Cells (Allogenic Ex Vivo Expanded Gamma Delta T Cells), Dinutuximab, Temozolomide, and Zoledronate for the Treatment of Refractory, Relapsed, or Progressive Neuroblastoma in Children

Active:	Yes
Cancer Type:	Neuroblastoma	NCT ID:	NCT05400603
Trial Phases:	Phase I	Protocol IDs:	AFLAC5537-22 (primary) NCI-2022-01839 STUDY00003123
Eligibility:	12 Months and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Emory University Hospital/Winship Cancer Institute
NCI Full Details:	http://clinicaltrials.gov/show/NCT05400603

Summary

This phase I trial studies the side effects and best dose of donor immune cells (allogenic ex vivo expanded gamma-delta T cells) when given together with dinutuximab, temozolomide, and zoledronate in treating children with neuroblastoma that does not respond to treatment (refractory), that has come back (relapsed), or that is growing, spreading, or getting worse (progressive). Donor gamma-delta T cells are immune cells taken from a healthy donor and infused back into the body for treatment. Donor gamma-delta T cells work in the body by activating the body's immune system to create more healthy cells that will directly kill the tumor cells. Dinutuximab is a drug that has been approved by the Food and Drug Administration (FDA) for treating newly diagnosed patients with neuroblastoma who complete other therapy and it has also been used to treat patients with relapsed/ refractory neuroblastoma. It is a monoclonal antibody. Monoclonal antibodies are proteins made in the laboratory (lab), designed to attach to specific targets on cancer cells. Dinutuximab was designed to attach to a target called GD-2 that is common on neuroblastoma cells. When dinutuximab attaches to the GD-2 target on neuroblastoma cells, the gamma-delta T cells can be stimulated to attack and kill the neuroblastoma cells. Temozolomide is a chemotherapy that is commonly given to neuroblastoma patients at relapse. Clinical trials showed that patients had much better tumor responses to dinutuximab given with temozolomide compared to other dinutuximab combinations in the same study, leading to this combination being studies in patients with newly diagnosed high risk neuroblastoma. Zoledronate is a drug given by intravenous (IV) that has been approved by the FDA for the treatment of other cancers. Zoledronate has also been used and safely given to children with solid tumor cancers such as neuroblastoma. Zoledronate has been found in lab tests to make gamma-delta T cells more active in killing neuroblastoma tumor cells. Giving donor gamma-delta T cells dinutuximab, temozolomide, and zoledronate may work better in treating children with refractory, recurrent, or progressive neuroblastoma.

Objectives

PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of allogeneic expanded gamma-delta T cells when delivered with dinutuximab, temozolomide, and zoledronic acid (zoledronate) in children with refractory, recurrent, or progressive neuroblastoma.
II. To define the toxicities of allogeneic expanded gamma-delta T cells when delivered with dinutuximab, temozolomide, and zoledronate.

SECONDARY OBJECTIVE:
I. To estimate, within the context of a phase I study, the clinical response rate to this combination regimen in patients with recurrent, refractory, or progressive neuroblastoma.

EXPLORATORY OBJECTIVES:
I. To determine if exhaustion markers (PD1, PDL-1, TIM3, TIGIT, LAG3, CD39) of the expanded product taken before freezing correlate with response and retention of product.
II. To determine if gamma-delta T cell-resident phenotypes correlates with response to therapy.
III. To determine the half-life of allogeneic gamma-delta T cells in the patient when given in this regimen.
IV. To determine effects on the innate immune system following treatment with dinutuximab, temozolomide, zoledronate and allogeneic gamma-delta T cells.

OUTLINE: This is a phase I dose-escalation study of allogeneic expanded gamma-delta T cells followed by a dose-expansion study.

Patients receive temozolomide orally (PO) on days 1-5, dinutuximab intravenously (IV) over 10 hours on days 2-5, zoledronate IV on day 5, and allogeneic expanded gamma-delta T cells on days 6 and 13 for over 5-15 minutes. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed for 1 year.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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