Gliomatosis Cerebri Clinical Trials

• Age:

• Participants must be age ≤ 21 years at initial diagnosis. Participants must be \>12 months of age at enrollment. Safety Run-In (first 6 participants) must be age 6 years or older. As of 09Jun2026 the safety run-in is complete.

• Pathology: All participants must have a pathologically confirmed diagnosis of neuroblastoma at any point in their treatment.

• Tumor assessment: Disease staging must be performed. This disease assessment is required for eligibility and must be done within a maximum of 4 weeks before first dose of study drug.

• Disease Status: Relapsed/Refractory Neuroblastoma Relapsed disease defined as neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) and has now relapsed and is in any number of relapses.

• Refractory disease defined as High-risk neuroblastoma as defined by the International Neuroblastoma Risk Group Staging System (INRG) that failed to achieve complete response (CR) after at least 4 cycles of aggressive multi-drug induction chemotherapy, progression during upfront therapy, or with disease remaining after standard immunotherapy.

• INRG High Risk NB defined as one of the following:

‣ Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification

‣ Age ≥ 547 days and INRG Stage M regardless of biologic features

‣ Any age initially diagnosed with INRG Stage L1 MYCN amplified neuroblastoma (NBL) who have progressed to Stage M without systemic chemotherapy

‣ Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy

• Measurable Disease: Participants must be relapsed or refractory with active disease. Participants must have measurable or evaluable disease, including at least one of the following: Measurable tumor \>10mm by computed tomography scan (CT) or magnetic resonance imaging (MRI); a positive metaiodobenzylguanidine (MIBG) scan or positron emission tomography (PET) scan or Positive bone marrow biopsy/aspirate.

• Cohort 1- High-risk neuroblastoma patients with disease limited to bone and/or bone marrow at enrollment. Participant must have stable disease, minor response, or partial response to their most recent therapy.

• Cohort 2- All other high-risk relapsed or refractory neuroblastoma patients not eligible for Cohort 1, including participants with soft tissue disease.

• Participants with central nervous system (CNS) disease currently taking steroids must have been on a stable dose of steroids for at least one week prior to their biopsy and must not have progressive hydrocephalus at enrollment.

• Timing from prior therapy:

• Participants must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

‣ Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).

‣ Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.

‣ Small Molecule Inhibitors (anti-neoplastic agent): At least 7 days since the completion of therapy with a small molecule inhibitor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.

‣ Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells, anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.).

‣ XRT (Radiotherapy): At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.

‣ Stem Cell Transplant:

⁃ Allogeneic: No evidence of active graft vs. host disease

• Allo/Auto: ≥ 2 months must have elapsed since transplant.

‣ MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.

• Participants must have a Lansky or Karnofsky Performance Scale score of ≥ 50

• Participants must have adequate organ function at the time of enrollment:

∙ Hematological: Hematological recovery as defined by absolute neutrophil count (ANC) ≥750/μL, platelets ≥30/μL (may be transfused).

‣ Liver: Normal liver function as defined by Aspartate transferase (AST), Alanine transaminase (ALT), and total bilirubin (TBL) all within upper limit of normal

‣ Renal:

⁃ For participants \< 17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr

• For participants ≥17 years old: estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: \[(140-age) x (Wt in kg) x (0.85 if female)\] / (72 x SCr)

‣ Cardiac: Participants must have a QTcF ≤ 470 msc.

⁃ Participants of childbearing potential must have a negative pregnancy test. Participants of childbearing potential must agree to use an effective birth control method.

⁃ Participants who are lactating must agree to stop breast-feeding. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)

⁃ Written informed consent in accordance with institutional and FDA guidelines must be obtained from all participants (or participants' legal representative).