A Phase II Study With a Safety Run-In of the Addition of N-803 to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma
2 other identifiers
interventional
54
1 country
4
Brief Summary
The study participant is being asked to take part in this research study because the participant has been diagnosed with neuroblastoma that did not fully respond to previous treatment (refractory), or it has returned after treatment (relapsed). Primary Aims
- To evaluate if the administration of N-803 in combination with irinotecan, temozolomide, hu14-18K322A, and GM-CSF in patients with relapsed/refractory neuroblastoma is feasible and tolerable
- To determine if the response rate of N-803 with irinotecan, temozolomide, hu14.18K322A and GM-CSF in patients with relapsed/refractory neuroblastoma is superior to the combination of irinotecan, temozolomide, hu14.18K322A, and GM-CSF Secondary Aims
- To describe the toxicity profile of N-803 administered with irinotecan, temozolomide, hu14.18K322A and GM-CSF
- To evaluate and compare the progression free survival (PFS) and overall survival (OS) of and between patients receiving irinotecan, temozolomide, hu14.18K322A and GM-CSF with and without N-803
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2025
Typical duration for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 9, 2025
CompletedFirst Posted
Study publicly available on registry
July 25, 2025
CompletedStudy Start
First participant enrolled
November 10, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2029
June 4, 2026
June 1, 2026
2.2 years
April 9, 2025
June 3, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
To evaluate if the administration of N-803 in combination with irinotecan, temozolomide, hu14-18K322A, and GM-CSF in patients with relapsed/refractory neuroblastoma is feasible
Feasibility Measures: Patients evaluable for toxicity in the safety run-in must receive one dose of N-803. The proportion of evaluable patients who successfully complete the protocol-defined treatment regimen in the Safety Run-in phase will be calculated. The reasons for treatment discontinuation or deviations from the protocol will be summarized.
Complete Cycle 1 treatment (each cycle is 21 days)
To determine if the response rate of N-803 with irinotecan, temozolomide, hu14.18K322A and GM-CSF in patients with relapsed/refractory neuroblastoma is superior to the combination of irinotecan, temozolomide, hu14.18K322A, and GM-CSF
Tolerability Assessments: Tolerability of the protocol-defined treatment in the Safety Run-in phase will be determined by assessing adverse events and their severity. Adverse events will be categorized based on standard CTCAE v5.0 criteria. Dose modifications or interruptions resulting from treatment-related adverse events will be analyzed.
Complete Cycle 1 treatment (each cycle is 21 days)
To determine if the response rate of N-803 with irinotecan, temozolomide, hu14.18K322A and GM-CSF in patients with relapsed/refractory neuroblastoma is superior to the combination of irinotecan, temozolomide, hu14.18K322A, and GM-CSF
Tumor response will be assessed using standard NANT criteria. The primary endpoint for response analysis will be Best Overall Response (BOR), defined as the best response observed prior to progression, cross over or start of another therapy. Point estimates for the response rate (proportion of patients who have BOR of PR or better) will be calculated, together with exact 95% confidence intervals.
Up to 10 cycles of irinotecan/temozolomide/hu14.18K322A/GM-CSF with or without N-803 in the Phase 2 (each cycle is 21 days)
Secondary Outcomes (3)
To describe the toxicity profile of N-803 administered with irinotecan, temozolomide, hu14.18K322A and GM-CSF
Up to 10 cycles of irinotecan/temozolomide/hu14.18K322A/GM-CSF with or without N-803 in the Phase 2 (each cycle is 21 days)
To evaluate and compare the progression free survival (PFS) of and between patients receiving irinotecan, temozolomide, hu14.18K322A and GM-CSF with and without N-803
Time from enrollment (phase I) or randomization (phase II) to disease progression, death, or last follow-up, whichever is earlier, assessed up to 36 months
To evaluate and compare overall survival (OS) of and between patients receiving irinotecan, temozolomide, hu14.18K322A and GM-CSF with and without N-803
Time from date of enrollment (phase I) or randomization (phase II) until the date of death from any cause, or last follow-up, whichever is earlier, assessed up to 36 months.]
Study Arms (3)
Chemoimmunotherapy
EXPERIMENTALPatients will be randomized to receive chemoimmunotherapy alone.
Chemoimmunotherapy + N-803
EXPERIMENTALPatients will be randomized to receive chemoimmunotherapy plus N-803.
Safety Run-In Treatment Schedule - Chemoimmunotherapy + N-803
EXPERIMENTALThe first 6 patients included in the safety assessment run-in phase will receive cycles of irinotecan, temozolomide, hu14.18K322A, GM-CSF and N-803. If fewer than 2 patients in the first cohort of 6 patients experience a DLT in Cycle 1, then the trial will proceed to Phase 2. If 2 or more of the first 6 patients experience a DLT in Cycle 1 then the N-803 will be dose reduced to 15 mcg/kg and 6 more patients will be enrolled in the safety assessment run-in. Once the safety assessment run-in phase is completed, patients will be enrolled onto the phase 2 study.
Interventions
IV, Days 1-5
IV, Days 1-5
IV over 4 hours daily times 4 doses, Days 2-5.
Subcutaneous (SC), Day 6.
Subcutaneous injection (preferred) or IV, Days 7-13.
Eligibility Criteria
You may qualify if:
- Age
- \- Patients must be \< 30 at the time of enrollment on study.
- Diagnosis
- \- Patients must have had histologic verification of neuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary or serum catecholamines \[i.e., \> 2 x upper limit of normal (ULN)\], at the time of initial diagnosis.
- Disease Risk Group
- Patients must have high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients whose disease was initially considered low or intermediate risk but were then reclassified as high-risk neuroblastoma prior to enrollment are also eligible.
- Response to Prior Therapy (using INRC definitions)
- \- Patients must have at least ONE (recurrent/progressive, refractory, or persistent) of the following:
- Recurrent/progressive disease after the diagnosis of high-risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy. (Note that this excludes patients initially considered low or intermediate risk that progressed to high-risk disease but have not progressed after the diagnosis of high-risk neuroblastoma).
- Refractory disease: A best overall response of no response/stable disease since diagnosis of high-risk neuroblastoma AND after at least 4 cycles of induction therapy.
- Persistent disease: A best overall response of partial response since diagnosis of high-risk neuroblastoma AND after at least 4 cycles of induction therapy
- Sites of Disease
- \- Patients must have at least ONE of the following (lesions may have received prior radiation therapy if they meet the other criteria listed below) based on institutional assessment:
- Bone Sites
- MIBG avid tumors: patients must meet one of the following criteria:
- +63 more criteria
You may not qualify if:
- \- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this study due to risks of fetal and teratogenic adverse events. Females of childbearing potential must have a negative pregnancy test to be eligible for this study.
- \- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- \- Patients with disease of any major organ system that would compromise their ability to withstand therapy.
- \- Patients who have undergone a prior allogeneic stem cell or solid organ transplant.
- \- Patients who are on hemodialysis.
- \- Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria.
- \- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicions.
- \- Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of reactive airway disease is permitted, as is the use of physiological doses of steroids for patients with known adrenal insufficiency.
- \- Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) are not eligible.
- \- Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible.
- \- Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible.
- \- Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
- \- Patients with symptoms of congestive heart failure are not eligible.
- \- Patients must not have \> Grade 2 diarrhea.
- \- Patients with a history of progressive disease while receiving therapy per ANBL1221 (irinotecan/temozolomide/dinutuximab/GMCSF).
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
University of California San Francisco
San Francisco, California, 94158, United States
Children's Hospital of Colorado
Colorado Springs, Colorado, 80902, United States
Motts Childrens Hospital
Ann Arbor, Michigan, 48109, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sara Federico, MD
St. Jude Children's Research Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 9, 2025
First Posted
July 25, 2025
Study Start
November 10, 2025
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
February 1, 2029
Last Updated
June 4, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.