Naxitamab, Irinotecan Hydrochloride, Temozolomide, and Sargramostim in Treating Patients with High-Risk Neuroblastoma
- Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the Memorial Sloan-Kettering [MSK] Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
- High-risk NB as defined as any of the following: * Stage 4 with MYCN amplification (any age) * Stage 4 without MYCN amplification (> 1.5 years of age) * Stage 3 with MYCN amplification (unresectable; any age) * Stage 4S with MYCN amplification (any age)
- Patients must fulfill one of the following criteria: * Have evidence of soft tissue disease OR * If they only have osteomedullary disease at protocol enrollment, they should have: ** Had previously received Hu3F8+GMCSF therapy AND have had less than a complete response to it OR ** Had progressive disease after their most recent anti-neuroblastoma therapeutic regimen
- Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive metaiodobenzylguanidine [MIBG] or positron emission tomography [PET] scans) or measurable (computed tomography [CT], magnetic resonance imaging [MRI]) disease documented after completion of prior systemic therapy
- Prior treatment with murine and hu3F8 is allowed
- Prior treatment with irinotecan or temozolomide is permitted
- Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative human anti-human antibody (HAHA) antibody titer; human anti-mouse antibody positivity is allowed
- Signed informed consent indicating awareness of the investigational nature of this program
- Patients with complete response (CR)/very good partial response (VGPR) disease
- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity >= grade 3 except for hearing loss, alopecia, anorexia, nausea, and hypomagnesemia from total parenteral nutrition (TPN), which may be grade 3
- Absolute neutrophil count (ANC) < 500/uL
- Platelet count < 30 K/uL
- History of allergy to mouse proteins
- Active life-threatening infection
- Inability to comply with protocol requirements
- Women who are pregnant or breast-feeding
I. To evaluate the safety of the combination of irinotecan hydrochloride (irinotecan), temozolomide, naxitamab (hu3F8) and sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]) (HITS) in patients with neuroblastoma (NB).
I. To evaluate tumor responses to HITS in patients with NB.
II. To evaluate pharmacokinetics of hu3F8.
III. To evaluate natural killer (NK) cell activation in patients treated with HITS.
IV. To evaluate serum cytokines in patients receiving HITS.
I. To evaluate minimal residual disease (MRD) changes in in bone marrow (BM).
Patients receive irinotecan hydrochloride intravenously (IV) over 60 minutes on days 1-5, temozolomide orally (PO) or IV on days 1-5, naxitamab IV over 30-90 minutes on days 2, 4, 8, and 10, and sargramostim subcutaneously (SC) on days 6-10. Cycles repeat every 21-42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 42 days.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
- Primary ID 17-251
- Secondary IDs NCI-2017-01143
- Clinicaltrials.gov ID NCT03189706