Hu3F8 + GM-CSF for Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Major organ dysfunction, Infection, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 10 days per cycle

186 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is safe for treating neuroblastoma.

Will I have to stop taking my current medications?

The trial requires that you stop any chemotherapy or immunotherapy at least three weeks before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment Hu3F8 + GM-CSF for neuroblastoma?

Research shows that the combination of anti-G(D2) antibody 3F8 and GM-CSF is highly effective against neuroblastoma, especially in cases resistant to other treatments. In a study, patients treated with this combination had a significantly better progression-free survival rate compared to those who received a different form of GM-CSF, indicating its potential effectiveness. ^{1 2 3 4 5}

Is the combination of Hu3F8 and GM-CSF safe for treating neuroblastoma?

The combination of Hu3F8 (an anti-GD2 antibody) and GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) has been studied in patients with neuroblastoma, showing manageable toxicities that allow outpatient treatment. Common side effects include decreased blood cell counts and fever, but these are generally considered manageable. ^{1 3 4 5 6}

How is the drug Hu3F8 + GM-CSF unique for treating neuroblastoma?

The drug Hu3F8 combined with GM-CSF is unique because it uses a specific antibody targeting GD2, a molecule found on neuroblastoma cells, and is administered with GM-CSF to enhance the immune response. This combination has shown improved progression-free survival rates compared to previous methods, particularly when GM-CSF is given under the skin rather than intravenously. ^{1 4 5 7 8}

Research Team

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients over 1 year old with high-risk neuroblastoma, which hasn't responded to standard treatments or has come back. They must have a certain number of white blood cells and not be allergic to mouse proteins. Pregnant or breastfeeding women can't join, nor can those with major organ problems (except hearing loss) or active severe infections.

Inclusion Criteria

I am older than 1 year.

My neuroblastoma is not responding to initial treatments or has come back.

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

Exclusion Criteria

Pregnant women or women who are breast-feeding.

My major organs are functioning well, except possible hearing loss or blood issues.

I have tested positive for HAHA antibodies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of iv hu3F8 in combination with sc GM-CSF over a treatment cycle of 10 days

10 days per cycle

3 visits (in-person) for hu3F8 administration

Expansion Phase II

Participants continue to receive treatment cycles every 1-2 months for up to 24 months or until 5 cycles post-major response

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• GM-CSF
• Hu3F8

Trial Overview The study tests the safety of combining an antibody called Hu3F8 with GM-CSF in treating neuroblastoma. It's looking at how well these two work together against cancer that's hard to treat or has returned after previous treatment.

Participant Groups

Group I: expansion phase II single arm trial Experimental Treatment 1 Intervention

Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123\^I-MIBG scan. Group 2 patients are in \>2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123\^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol.

Group II: Hu3F8 with GM-CSF Experimental Treatment 1 Intervention

The phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 \& 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is 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

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]

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

Early molecular response of marrow disease to biologic therapy is highly prognostic in neuroblastoma. [2019]

3. 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]

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

Phase II trial of the anti-G(D2) monoclonal antibody 3F8 and granulocyte-macrophage colony-stimulating factor for neuroblastoma. [2020]

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

Key role for myeloid cells: phase II results of anti-G(D2) antibody 3F8 plus granulocyte-macrophage colony-stimulating factor for chemoresistant osteomedullary neuroblastoma. [2021]

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

A Phase I/IIa Study of Antidisialoganglioside Antibody Dinutuximab in Japanese Patients With Neuroblastoma. [2023]

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

MYCN-amplified stage 2/3 neuroblastoma: excellent survival in the era of anti-GD2 immunotherapy. [2019]

8. England pubmed.ncbi.nlm.nih.gov

G-CSF as a suitable alternative to GM-CSF to boost dinutuximab-mediated neutrophil cytotoxicity in neuroblastoma treatment. [2022]