Phase I Trial of rhIL-15 Plus Dinutuximab Plus Irinotecan/Temozolomide for Children and Young Adults With Relapsed/Refractory Neuroblastoma

Description

BACKGROUND:

Neuroblastoma is the most common extracranial pediatric solid tumor, accounting for approximately 15 percent of all childhood cancer-related deaths. Neuroblastoma predominantly affects infants and toddlers and manifests as a solid tumor of the parasympathetic ganglia. Despite multi-modal therapy including multiagent induction chemotherapy, surgery, consolidation with tandem autologous bone marrow transplantation, radiation, anti-GD2 antibody therapy plus GMCSF, and differentiation therapy with cis-retinoic acid, less than 30 percent of newly-diagnosed patients with high-risk neuroblastoma attain long-term remissions, highlighting the need for new and more effective therapies. Based on our preclinical studies, we are proposing in this study, to evaluate recombinant human interleukin (IL)-15 (rhIL-15) with the FDA-approved anti-GD2 antibody, dinutuximab, and chemotherapy (i.e., irinotecan and temozolomide) in children with relapsed/refractory neuroblastoma with the goal to evaluate the safety, toxicity and RP2D of rhIL-15 as part of this chemo-immunotherapy regimen.

OBJECTIVES:

* Primary Objective

— Assess the safety of rhIL-15 combined with dinutuximab and irinotecan/temozolomide in pediatric and young adult participants with recurrent or refractory neuroblastoma by determining the recommended phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) of defined adverse events (AEs).
* Secondary Objectives

* Assess the preliminary anti-tumor activity of rhIL-15 when added to a regimen with dinutuximab/temozolomide/irinotecan in children and young adults with relapsed and/or refractory neuroblastoma.
* Assess the pharmacokinetics of rhIL-15 when given with dinutuximab.
* Exploratory Objectives

* Determine the function and kinetics of natural killer (NK) cells and CD8 T cells in the peripheral blood after therapy with rhIL-15 and dinutuximab.
* Determine if plasma cell free DNA (cfDNA) correlates with tumor burden and response
* Evaluate tumor heterogeneity pre/post chemo-immunotherapy in bone marrow samples if tumor present.