NCT06995872

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 3 Years – 35 Years
• Healthy volunteers: Not accepted

Summary

Background: Neuroblastoma is a type of cancer that causes tumors in nerves. It affects mainly infants and toddlers, and it causes about 15 percent of cancer-related deaths in children. Objective: To test a new drug (rhIL-15), combined with 3 standard cancer drugs, in people with neuroblastoma. Eligibility: People aged 3 to 35 years with neuroblastoma that did not respond or returned after standard treatment. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of their heart and lungs. They will have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle. Participants will be treated in 21-day cycles. They may have up to 4 treatment cycles. rhIL-15 is given through a needle into a vein over 5 to 7 days during the first week of each cycle. Participants will stay in the hospital while they are receiving the rhIL-15. Starting in the second week of the second cycle, participants will receive other drugs for treating cancer. They will have no study treatments during the third week of each cycle. Participants will visit the clinic at least 2 times a week throughout all 4 treatment cycles. They will have a physical exam and blood tests during these visits. Imaging scans, bone marrow biopsy, and other tests will be repeated at the end of cycles 2 and 4. Participants will have a follow-up visit 6 months after treatment ends. This visit will include a physical exam with blood and urine tests.

Detailed 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.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	rhIL-15	rhIL-15 will be given at a dose of 0.13-2 mcg/kg/day (based on dose level) as a continuous IV infusion for 5 days each cycle.
DRUG	Dinituximab	Dinituximab will be given at a dose of 17.5 mg/m\^2/dose by IV on days 2-5 of each cycle.
DRUG	Temozolomide	Temozolomide will be given orally (PO) at a dose based on weight on days 1-5 of each cycle beginning with cycle 2.
DRUG	Irinotecan Hydrochloride	Irinotecan will be given at a dose of 50 mg/m\^2/dose by IV on days 1-5 of each cycle beginning with cycle 2.

Timeline

• Start date: 2025-10-21
• Primary completion: 2028-06-01
• Completion: 2029-06-01
• First posted: 2025-05-30
• Last updated: 2026-04-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study