This phase I trial tests the safety, side effects and best dose of recombinant human (rh) interleukin (IL)-15 when given with dinutuximab, irinotecan and temozolomide for the treatment of children and young adults with neuroblastoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). RhIL-15 is a man-made version of a small protein (cytokine) that is naturally produced in the body by certain white blood cells and increases the activity and strength of the immune system and may also activate immune cells to kill neuroblastoma cells. Dinutuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving rhIL-15 with dinutuximab, irinotecan and temozolomide may be safe, tolerable and/or effective in treating patients with children and young adults with relapsed or refractory neuroblastoma.
Additional locations may be listed on ClinicalTrials.gov for NCT06995872.
Locations matching your search criteria
United States
Maryland
Bethesda
National Institutes of Health Clinical CenterStatus: Active
Contact: Site Public Contact
Phone: 800-411-1222
PRIMARY OBJECTIVE:
I. 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:
I. 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.
II. Assess the pharmacokinetics of rhIL-15 when given with dinutuximab.
EXPLORATORY OBJECTIVES:
I. 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.
II. Determine if plasma cell free deoxyribonucleic acid (cfDNA) correlates with tumor burden and response.
III. Evaluate tumor heterogeneity pre/post chemo-immunotherapy in bone marrow samples if tumor present.
OUTLINE:
Patients receive rhIL-15 intravenously (IV) continuously on days 1-5 of week 1 and dinutuximab IV over 10-20 hours on days 2-5 of week 1 of each cycle. Starting with cycle 2, patients also receive irinotecan IV over 90 minutes and temozolomide orally (PO) via nasogastric (NG) or gastric tube (G-tube) once daily (QD) on days 1-5 of week 2 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspirate and biopsy, echocardiography, magnetic resonance imaging (MRI) and blood sample collection throughout the study and may undergo Iodine I 123-metaiodobenzylguanidine (123 I-MIBG) computed tomography (CT) scan, positron emission tomography (PET)/CT scan and/or CT scan throughout the study.
After completion of study treatment, patients are followed up at 6 months.
Lead OrganizationNCI - Center for Cancer Research
Principal InvestigatorHong Ha Rosa Nguyen