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

NCT ID: NCT02650648

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-05
• Study Completion Date: 2025-07-28

Brief Summary

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

Conditions

Neuroblastoma; High-Risk

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

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).

NK cells

Intervention Type: BIOLOGICAL

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.

hu3F8

Intervention Type: BIOLOGICAL

On Days -1, +1, +5, +7 and +9 hu3F8 is administered at 1.68 mg/kg/day and infused over \~30-90 minutes

rIL-2

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: DRUG

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.

Intervention Type: 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

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Other Intervention Names

Cytoxan®

Eligibility Criteria

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 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

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Y-mAbs Therapeutics

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shakeel Modak, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

https://www.mskcc.org/

Memorial Sloan Kettering Cancer Center

Other Identifiers

5415

Identifier Type: OTHER

Identifier Source: secondary_id

15-272

Identifier Type: -

Identifier Source: org_study_id