NeuroblastomaPhase 1NCT06995872
Phase I Trial of rhIL-15 Plus Dinutuximab Plus Irinotecan/Temozolomide for Children and Young Adults With Relapsed/Refractory Neuroblastoma
A Phase 1 study testing rhIL-15, Dinituximab and Temozolomide in people with Neuroblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 35 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- rhIL-15, Dinituximab and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2025to 1 Jun 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Presence of pericardial effusion.
- Chronic immunosuppression (physiologic steroid supplementation is allowed but any chronic immunosuppressant like steroids or other modulators are not allowed)
- Major surgery within 4 weeks prior to initiation of study therapy
- Current/active human immunodeficiency virus (HIV) infection, as measured by seropositivity for HIV antibody.
- Current/active HBV/HCV infection as measured by seropositivity for Hepatitis C or positive for Hepatitis B surface antigen (HBsAg).
- History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biological composition to irinotecan and temozolomide used in study.
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- Participants with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
- Positive serum or urine beta-HCG pregnancy test performed at screening due to the teratogenic effects of chemotherapy.
- Participants with a prior or concurrent malignancy whose natural history or treatment with the safety or efficacy assessment of the investigational regimen.
- Participants with >= grade 2 diarrhea at the time of entry.
- Participants who are unable to tolerate oral/nasogastric/gastrostomy medications. Additionally, participants with significant malabsorption will not be eligible for this trial.
- Participants with uncontrolled infection.
- Participants with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NCI Referral Office, 1-888-NCI-1937, ncimo_referrals@mail.nih.gov
About this study
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.
Read more
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.
Read the 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.
- Determine patient-reported outcomes (PRO) during treatment.
- Conditions
- Neuroblastoma
- Being tested
- rhIL-15, Dinituximab, Temozolomide, Irinotecan Hydrochloride
- Keywords
- Irinotecan, Temozolomide, ch14.18, IL-15, Neuroblastoma, Dinituximab
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhIL-15Drug
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.
DinituximabDrug
Dinituximab will be given at a dose of 17.5 mg/m^2/dose by IV on days 2-5 of each cycle.
TemozolomideDrug
Temozolomide will be given orally (PO) at a dose based on weight on days 1-5 of each cycle beginning with cycle 2.
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Participants will receive dinutuximab at a dose of 17.5 mg/m2/day x 4 days, in combination with escalating doses of rhIL-15 and fixed dose irinotecan and temozolomide. Receives: Drug: rhIL-15; Drug: Dinituximab; Drug: Temozolomide; Drug: Irinotecan Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the safety and determine the MTD of rhIL-15 combined with dinutuximab/temozolomide/irinotecan
Assessment of AEs and DLTs in participants.
Measured: 6 weeks
Secondary outcomes (2)
Anti-tumor activity
Response will be evaluated by applying the INRC after even numbers of cycles. This includes response at the following sites: Primary tumor, metastatic soft tissue and bone site, bone marrow.
Measured: 6 months
Pharmacokinetics
rhIL-15 levels in the plasma of participants at various timepoints after initiation of the rhIL-15 infusion.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start21 Oct 2025
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Hong Ha Rosa Nguyen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06995872
- Sponsor's protocol ID
- 10001842
- Other IDs
- 001842-C
- Status last verified
- 19 Oct 2026
- First submitted
- 28 May 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.