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

Recruiting now · Phase 2

Conditions studied: Neuroblastoma Recurrent

In brief

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

Key facts

Study ID

NCT07085338

Run by

St. Jude Children's Research Hospital

People needed

54

Starts

2025-11-10

Expected to finish

2029-02-01

Last updated by the study team

2026-08-07

Who can join

Age: any, up to 30. Sex: any. Healthy volunteers: not accepted.

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:
• a. Patients with recurrent/progressive or refractory disease: i. Must have at least one MIBG avid bone site on planar imaging OR ii. Must have > 2 lesions on SPECT/CT. A biopsy is not required unless the above imaging criteria are not met
• b. Patients with persistent disease: i. If a patient has 3 or more MIBG avid bone lesions, then no biopsy is required.
• ii. If a patient has only 1 or 2 MIBG avid bone lesion sites, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required. Bone lesions may be biopsied at any time point prior to enrollment.
• For MIBG non-avid tumors, patients must have at least an FDG-PET avid site and meet the following criteria:
• Biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment of at least one FDG-PET avid site.
• Bone Marrow
• Any amount of tumor cells in the bone marrow (including neuroblasts, mature and maturing ganglion cells) done at the time of study enrollment based on routine morphology and/or immunohistochemistry in at least one sample from bilateral aspirates and biopsies. NOTE: Patients with bone marrow disease only will be eligible if they have more than 5% disease involvement (documented neuroblastoma cells) in at least one sample from bilateral bone marrow biopsies.
• Soft Tissue Sites
• At least one soft tissue lesion that meets criteria for a TARGET lesion as defined by:
• SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for discrete lymph nodes ≥ 15mm on short axis. Lesions meeting size criteria will be considered measurable.

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).
• Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
• Patients with elevated catecholamines (i.e., > 2 x ULN) only and no evidence of disease are NOT eligible for this study.

Where it is running

• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (enrolling)
• University of California San Francisco — San Francisco, California, United States
• Children's Hospital of Colorado — Aurora, Colorado, United States
• Motts Childrens Hospital — Ann Arbor, Michigan, United States

Full record on ClinicalTrials.gov

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