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

85 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the treatment Hu3F8 + NK Cells for High-Risk Neuroblastoma?

Research shows that NK cells combined with anti-GD2 antibodies, like m3F8, have shown anti-neuroblastoma activity, especially at higher doses, and are safe to use. Cyclophosphamide, a part of the treatment, has been shown to enhance immune responses in neuroblastoma, suggesting potential benefits when combined with other therapies. ^{1 2 3 4 5}

Is the combination of hu3F8 and NK cells safe for treating high-risk neuroblastoma?

The combination of hu3F8 and NK cells has been shown to be generally safe in humans, with one study reporting only one patient experiencing serious side effects like high blood pressure and lung inflammation. Another study found that combining NK cells with chemotherapy and a similar antibody treatment was feasible, though some patients experienced common side effects like low blood cell counts and mild pain. ^{1 4 6 7 8}

How is the Hu3F8 + NK Cells treatment different from other treatments for high-risk neuroblastoma?

The Hu3F8 + NK Cells treatment is unique because it combines a monoclonal antibody (hu3F8) with natural killer (NK) cells to target neuroblastoma cells, leveraging the immune system to attack the cancer. This approach is different from traditional chemotherapy as it specifically enhances the body's immune response against the tumor, potentially reducing the side effects associated with conventional treatments. ^{1 2 4 8 9}

Research Team

Shakeel Modak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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.

I have had treatments with specific antibodies and do not have HAHA antibodies.

Exclusion Criteria

I am not pregnant or breast-feeding.

ANC should be >500/uL

Platelet count >75K/uL.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy with haploidentical natural killer cells and Anti-GD2 monoclonal antibody m3F8 for resistant neuroblastoma: Results of a phase I study. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-2, and Haploidentical Natural Killer Cells. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide depletes tumor infiltrating T regulatory cells and combined with anti-PD-1 therapy improves survival in murine neuroblastoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A novel intensive induction therapy for high-risk neuroblastoma utilizing sequential peripheral blood stem cell collection and infusion as hematopoietic support. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma. [2022]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Ex vivo activation of CD56(+) immune cells that eradicate neuroblastoma. [2017]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells. [2021]