Hu3F8 + GM-CSF + Isotretinoin for Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Estimated 6-12 months

59 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test see the combined effects of the study drug called Humanized 3F8 (Hu3F8) when used with granulocyte-macrophage colony stimulating factor (GM-CSF). Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects.

Will I have to stop taking my current medications?

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 drug combination Hu3F8, GM-CSF, and Isotretinoin for treating neuroblastoma?

Research shows that combining anti-GD2 antibodies with GM-CSF and isotretinoin can improve outcomes for high-risk neuroblastoma patients, with studies reporting prolonged progression-free survival and overall survival rates. This combination has shown effectiveness in both preclinical and clinical settings, particularly in patients who have achieved a second remission. ^{1 2 3 4 5}

What is known about the safety of Hu3F8, GM-CSF, and Isotretinoin for neuroblastoma treatment?

The combination of anti-GD2 antibody (like Hu3F8), GM-CSF, and isotretinoin has been used in treating neuroblastoma, showing some treatment-related side effects. Common side effects include pain, fever, and infections, with some cases requiring intensive care, but no treatment-related deaths were reported. These side effects were generally manageable, allowing for outpatient treatment. ^{3 4 6 7 8}

How is the Hu3F8 + GM-CSF + Isotretinoin drug different from other neuroblastoma treatments?

The Hu3F8 + GM-CSF + Isotretinoin drug is unique because it combines a monoclonal antibody (Hu3F8) targeting GD2, a protein on neuroblastoma cells, with GM-CSF to boost the immune response, and isotretinoin to help prevent cancer recurrence, offering a novel approach compared to standard treatments. ^{3 4 9 10 11}

Research Team

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients with high-risk neuroblastoma, which includes certain stages of the disease and specific age groups. Participants must have a negative antibody test against Hu3F8 and be in their first complete or very good partial remission. They can't join if they have severe organ dysfunction, active serious infections, or can't follow the study plan.

Inclusion Criteria

My cancer is in its first complete or very good partial response.

My neuroblastoma diagnosis is confirmed by specific tests and high urine catecholamine levels.

My neuroblastoma is high-risk, either due to MYCN amplification or being over 18 months with stage 4.

Exclusion Criteria

Inability to comply with protocol requirements

I do not have severe organ problems, except possible hearing loss or blood issues.

I do not have a severe infection that is threatening my life.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Hu3F8/GM-CSF for 5 cycles and isotretinoin for 6 cycles. Isotretinoin starts after cycle 2 of Hu3F8/GM-CSF.

Estimated 6-12 months

Follow-up

Participants are monitored for relapse-free survival and safety for up to 2 years

2 years

Treatment Details

Interventions

• GM-CSF
• Hu3F8
• Isotretinoin

Trial Overview The study is looking at how well Humanized 3F8 (Hu3F8) works when combined with GM-CSF to prevent neuroblastoma from growing back after initial treatment success. Patients will also receive Isotretinoin as part of their therapy regimen.

Participant Groups

Group I: Hu3F8/GM-CSF Plus Isotretinoin Experimental Treatment 3 Interventions

In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF x5 cycles and isotretinoin x6 cycles. Isotretinoin starts after cycle 2 of hu3F8/GM-CSF.

GM-CSF is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Leukine for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma
• HIV Infection

Approved in European Union as Sargramostim for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma

Approved in Canada as Leukine for:

• Neutropenia
• Bone Marrow Transplantation
• Leukemia
• Lymphoma

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 combination treatment of irinotecan, temozolomide, dintuximab, and GM-CSF (I/T/DIN/GM-CSF) showed significant antitumor activity in patients with relapsed or refractory neuroblastoma, with an overall objective response rate of 41.5% across 53 patients.

The treatment was associated with a one-year progression-free survival rate of 67.9% and an overall survival rate of 84.9%, although it also resulted in notable grade ≥ 3 toxicities, including fever/infection and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. Mody, R., Yu, AL., Naranjo, A., et al.[2021]

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

References

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

Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group. [2023]

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

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. [2021]

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

Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Phase II Study. [2020]

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

Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. [2022]

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

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2 immunotherapy and isotretinoin: a prospective Phase II study. [2021]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment-Related Toxicities During Anti-GD2 Immunotherapy in High-Risk Neuroblastoma Patients. [2021]

9. France pubmed.ncbi.nlm.nih.gov

Dinutuximab: A Review in High-Risk Neuroblastoma. [2019]

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

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

11. 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]