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Naxitamab, Irinotecan Hydrochloride, Temozolomide, and Sargramostim in Treating Patients with High-Risk Neuroblastoma

Trial Status: Active

This phase II trial studies the side effects of naxitamab, irinotecan hydrochloride, temozolomide, and sargramostim in treating patients with high-risk neuroblastoma. Immunotherapy with naxitamab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as irinotecan hydrochloride, temozolomide, and sargramostim, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving naxitamab, irinotecan hydrochloride, temozolomide, and sargramostim may work better in treating patients with high-risk neuroblastoma.

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Shakeel Modak
Phone: 212-639-7623

PRIMARY OBJECTIVE:

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).

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVE:

I. To evaluate minimal residual disease (MRD) changes in in bone marrow (BM).

OUTLINE:

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

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Shakeel Modak

  • Primary ID 17-251
  • Secondary IDs NCI-2017-01143
  • Clinicaltrials.gov ID NCT03189706