Study of Chemoimmunotherapy for High-Risk Neuroblastoma

Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma

The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroblastoma (NB)
• Intervention / Treatment: Drug: Irinotecan; Drug: temozolomide; Biological: Hu3F8; Drug: GM-CSF

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of NB as defined by international criteria,.e., histopathology (confirmed by the 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 fulfill one of the following criteria:

  1. Have evidence of soft tissue disease OR

  2. 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 progressed progressive disease after their most recent anti-neuroblastoma therapeutic regimen
• Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, 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 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 CR/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 TPN, which may be grade 3
• ANC < 500/uL
• Platelet count <30K/uL
• History of allergy to mouse proteins
• Active life-threatening infection
• Inability to comply with protocol requirements
• Women who are pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS); Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.	Drug: Irinotecan; 50mg/m^2/day IV will be administered from day 1-5; Drug: temozolomide; (given concurrently with Irinotecan) 150mg/m^2/day orally; Biological: Hu3F8; 2.25mg/kg IV will be administered on days 2, 4, 8 and 10; Drug: GM-CSF; 250mcg/m2/day SC will be administered on days 6-10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	The regimen will be considered safe if there are no toxicities requiring discontinuation of therapy in at least 9/10 patients during the first two cycles.	2 years
response rate (CR+PR)	Response assessment will be based on the best response over the course of four cycles. Disease response for NB will use the International NB Response Criteria. Patients who withdraw from the study prior to cycle 4 with < partial response will also not be considered evaluable for response and will be replaced.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Y-mAbs Therapeutics
• Investigators: Principal Investigator: Shakeel Modak, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Temozolomide; Irinotecan; Sargramostim; Chemoimmunotherapy; Hu3F8; 17-251
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Irinotecan
• Other Study ID Numbers: 17-251

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No