Hu3F8 + NK Cells for High-Risk Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Severe organ dysfunction, Infection, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals with high-risk neuroblastoma, a type of cancer. It combines the chemotherapy drug cyclophosphamide with natural killer (NK) cells, a type of white blood cell, and an antibody known as Hu3F8. The primary goal is to determine if this combination is safe and can be administered successfully to patients. Ideal participants are those whose neuroblastoma has not responded well to standard treatments or has recurred. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using hu3F8 with NK cells appears safe. In one study involving 57 patients with high-risk neuroblastoma, high doses of hu3F8 were well tolerated. Patients did not require hospital stays for monitoring, indicating the treatment's manageability.

Another study found that using NK cells with a similar antibody, m3F8, was safe and had positive effects against neuroblastoma at higher doses.

These findings suggest that treatment with hu3F8 and NK cells might be safe for those considering joining a trial. However, ongoing research will provide more information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining hu3F8 with NK cells for high-risk neuroblastoma because this approach offers a unique mechanism of action. Unlike standard treatments, which often rely on chemotherapy alone, hu3F8 is a humanized antibody that targets GD2, a molecule commonly found on neuroblastoma cells. This allows the immune system to better recognize and attack the cancer. Additionally, the use of NK cells, which are a type of immune cell, enhances the body's ability to fight the cancer cells more effectively. This innovative combination aims to improve outcomes by directly engaging the immune system in a way that traditional therapies do not.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

Research has shown that hu3F8, a type of antibody, targets GD2, a molecule found on neuroblastoma cancer cells. In studies, hu3F8 has triggered the body's immune system to attack these cancer cells. In this trial, participants will receive hu3F8 combined with NK cells, a type of immune cell known for destroying neuroblastoma cells. Early findings suggest that combining NK cells with treatments like hu3F8 can effectively fight high-risk neuroblastoma. This combination aims to strengthen the body's natural defenses to combat the cancer more effectively. ^{1 2 6 7 8}

Who Is on the Research Team?

Shakeel Modak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and adults with high-risk neuroblastoma who haven't responded well to standard treatments. Participants need a compatible NK cell donor, must have evidence of persistent or progressing disease, and cannot be pregnant or breastfeeding. They should not have severe organ dysfunction or life-threatening infections.

Inclusion Criteria

Signed informed consent indicating awareness of the investigational nature of this program.

My neuroblastoma is considered high-risk based on its stage and MYCN gene status.

My cancer can be measured or seen on scans after my last treatment.

Exclusion Criteria

I am not pregnant or breast-feeding.

ANC should be >500/uL

Platelet count >75K/uL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive cyclophosphamide as part of the treatment protocol

1-2 weeks

Treatment

Participants receive NK cells and Hu3F8 antibody in sequential groups to assess safety and feasibility

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• cyclophosphamide
• hu3F8
• NK cells

Trial Overview The study tests the safety and feasibility of combining cyclophosphamide (chemotherapy), natural killer (NK) cells, and Hu3F8 antibody as a treatment for neuroblastoma. It's an early-phase trial to see how patients tolerate this approach before considering further studies.

How Is the Trial Designed?

Group I: Humanized Anti-GD2 Antibody Hu3F8 Experimental Treatment 4 Interventions

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.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Published Research Related to This Trial

The study evaluated hu14.18-IL2 in 27 pediatric patients with recurrent neuroblastoma and found it can be safely administered at a maximum tolerated dose of 12 mg/m2/d, with reversible toxicities similar to those seen in adult studies.

While no complete or partial responses were observed, treatment led to immune activation, indicating potential antitumor activity, and a phase II trial is planned to further assess its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Osenga, KL., Hank, JA., Albertini, MR., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6440722/

Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing ... In this phase 1 clinical trial of 57 patients with high-risk neuroblastoma, high doses of hu3F8 were well tolerated, without a need for inpatient monitoring.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02650648

NCT02650648 | Humanized Anti-GD2 Antibody Hu3F8 and ... 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5674972/

Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus ... 18, 75% of the patients never developed HAHA response even after getting more treatment cycles. Hu3F8 induced a de novo anti-GD2 response in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01662804

Humanized 3F8 Monoclonal Antibody (Hu3F8) When ... The purpose of this study is to find out if "humanized 3F8" (Hu3F8) when combined with interleukin-2 (rIL2) is safe for treating neuroblastoma and other ...

5. nature.com nature.com/articles/s41467-025-56619-x

The anti-GD2 monoclonal antibody naxitamab plus GM ... Naxitamab (previously called hu3F8) is a high-affinity, humanized monoclonal antibody (mAb) against GD2, a disialoganglioside implicated in the ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02650648/

Clinical Trial: NCT02650648 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, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6136849/

Adoptive immunotherapy with haploidentical natural killer ... Adoptive NK-cell therapy in combination with m3F8 is safe and has anti-neuroblastoma activity at higher cell doses. KEYWORDS: adoptive immunotherapy, m3F8, ...

8. clinicaltrial.be clinicaltrial.be/en/details/10558?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic ... 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 ...