Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

July 29, 2025 updated by: Memorial Sloan Kettering Cancer Center

Phase I Study of the Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

This is a phase I study. The purpose of this study is to see if it is safe and feasible to give the participant cyclophosphamide (a type of chemotherapy), natural killer (NK) cells, and an antibody called Hu3F8 as a treatment for neuroblastoma. NK cells are a type of white blood cell.

Funding Source- FDA OOPD

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

85

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Diagnosis of NB as defined by international criteria,.e., histopathology (confirmed by the MSKCC Department of Pathology) or bone marrow metastases plus high urine catecholamine levels.
  • High-risk NB as defined by risk-related treatment guidelines1 and the International NB Staging System, i.e., stage 4 with (any age) or without (>365 days of age) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage 4S.
  • Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy.
  • 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.
  • Disease staging approximately within one month of treatment
  • Prior treatment with murine and hu3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody (HAMA) positivity is allowed.
  • Eligible NK donor
  • Children and adults are eligible
  • Signed informed consent indicating awareness of the investigational nature of this program.

Donor Inclusion Criteria

  • Donor is blood-related and HLA-haploidentical to the recipient.
  • Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors. Tests include but are not limited to: Hepatitis B Surface Antigen, Hepatitis B Surface Antibody, Hepatitis B Core Antibody, Hepatitis C antibody, Epstein-Barr Virus Antibody, HIV, HTLV I and II, Varicella Zoster (Herpes Zoster), Herpes Simplex Antibody, Cytomegalovirus Antibodies, Syphilis (RPR profile) for adolescents and adults, measles for pediatric patients, West Nile Virus, Chagas screen, and Toxoplasma antibodies. Donor must have normal negative test results for HIV, HTLV I and II, and West Nile Virus. Donor exposure to other viral pathogens will be discussed on a case-by-case basis by investigators.
  • Donor must be able to undergo leukopheresis for total volume of 10-15 liters.
  • There is no age restriction for the donor.

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, hyperbilirubinemia and hypomagnesemia from TPN, which may be grade 3
  • ANC should be >500/uL
  • Platelet count >75K/uL.
  • History of allergy to mouse proteins
  • Active life-threatening infection
  • Inability to comply with protocol requirements
  • Women who are pregnant or breast-feeding

Donor Exclusion Criteria:

  • Cardiac risk factors precluding ability to undergo leukopheresis
  • Concurrent malignancy or autoimmune disease
  • Donor is pregnant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Humanized Anti-GD2 Antibody Hu3F8
This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with hu3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups with a minimum of 3 patients/ dose of NK cells. Three dose levels of NK cells, starting at dose level 1, will be evaluated in this treatment protocol. The goal dose for each dose level is the high boundary (e.g. 9.9x10^6/kg in level 1; 14.9x10^6/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved.
Drug: cyclophosphamide
chemotherapy with intravenous (IV) cyclophosphamide 50mg/kg/day (for patients with body weight<70kg) or 1500mg/m^2/day (for patients with body weight ≥70kg) for two days (days -6 and -5).
Other Names:
  • Cytoxan®
Biological: NK cells
Day 0: NK cell infusion. NK cells are resuspended in Normasol at a concentration no less than 5 x 10^6cells/mL. The patient is pre-medicated as per standard cell product infusion. The cell product is infused through a central venous catheter. Patients will be evaluated clinically by vital signs pre- and approximately 30 minutes post infusion of NK cells and thereafter at approximately 1 hour intervals for 4 hours.
Biological: hu3F8
On Days -1, +1, +5, +7 and +9 hu3F8 is administered at 1.68 mg/kg/day and infused over ~30-90 minutes
Drug: rIL-2
On day 0, daily from +2 through +4, day +6, and day +8, rIL-2 is administered subcutaneously at 6 x 10^5 U/m^2/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number patient responses observed at each dose level
Time Frame: 2 years
as defined by International NB Response Criteria. Disease status is defined by the International NB Response Criteria. Complete response/remission (CR): no evidence of disease. Very good partial response/remission (VGPR): >90% decrease in all disease parameters, except bone scan unchanged or improved; bone marrow must be free of disease. Partial response/remission: >50% decrease in all disease parameters, except bone scan unchanged or improved; no more than 1 positive bone marrow site. Mixed response: >50% decrease in >1 but not all disease markers. Stable disease: <50% decrease in all tumor markers. Progressive disease: new lesion, or >25 % increase in any disease marker.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2016

Primary Completion (Actual)

July 28, 2025

Study Completion (Actual)

July 28, 2025

Study Registration Dates

First Submitted

January 6, 2016

First Submitted That Met QC Criteria

January 6, 2016

First Posted (Estimated)

January 8, 2016

Study Record Updates

Last Update Posted (Actual)

July 30, 2025

Last Update Submitted That Met QC Criteria

July 29, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-272
  • 5415 (Other Identifier: OPD grant number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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