Hu3F8 + GM-CSF + Isotretinoin for Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Major organ dysfunction, Infection, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a combination of three treatments—Hu3F8, GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor), and isotretinoin—can stop neuroblastoma tumors from growing. Neuroblastoma typically affects young children. The study tests whether these medicines work well together and if they cause any side effects. Individuals diagnosed with high-risk neuroblastoma who are currently in a good response phase after initial treatment might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

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

Research has shown that the combination of Hu3F8, GM-CSF, and isotretinoin has been studied for safety in treating neuroblastoma, a type of cancer. A previous study found that Hu3F8, when used with GM-CSF, caused mild side effects and did not trigger a strong immune reaction against the treatment, indicating it is generally well-tolerated.

While Hu3F8 and GM-CSF may help stop neuroblastoma from growing, they can also cause side effects. Isotretinoin, a drug often used for severe acne, is known to be safe and has FDA approval for other uses.

Overall, this combination has shown promising safety results, but like any treatment, it may cause side effects. Participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Hu3F8, GM-CSF, and Isotretinoin for treating neuroblastoma because it approaches the disease with a unique strategy. Unlike traditional treatments that primarily focus on chemotherapy, this combination utilizes an antibody-based approach with Hu3F8, which targets cancer cells more precisely. The addition of GM-CSF boosts the immune response, potentially enhancing the body’s ability to fight off cancer cells. Isotretinoin, usually known for treating severe acne, is included for its ability to promote cell differentiation, which can help prevent cancer cells from multiplying. Together, these elements offer a multi-faceted approach, potentially leading to improved outcomes for patients with neuroblastoma.

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

Research has shown that a combination of three treatments—Hu3F8, GM-CSF, and isotretinoin—may be promising for treating neuroblastoma, a type of cancer. In this trial, patients will receive this combination, which studies have shown provides a 33% chance of their cancer not worsening over five years and a 48% chance of surviving for five years. This treatment delayed cancer progression and improved survival chances for nearly half of the patients. Hu3F8 targets cancer cells, GM-CSF strengthens the immune system, and isotretinoin, a form of vitamin A, helps stop cancer cells from growing. These findings suggest that this treatment might effectively control neuroblastoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03033303

NCT03033303 | A Study of the Effect of Hu3F8/GM-CSF ...

Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects. Official Title. Hu3F8/GM-CSF Immunotherapy Plus ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03033303?term=GM-CSF&aggFilters=status:not%20rec%20enr%20act&viewType=Table&rank=4

A Study of the Effect of Hu3F8/GM-CSF Immunotherapy ...

A Study of the Effect of Hu3F8/​ GM - CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma. ClinicalTrials.gov ID ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4485744/

Prolonged progression-free survival after consolidating ...

For the total of 101 study patients, 5-year PFS and overall survival (OS) rates were 33% ± 5% and 48% ± 5%, respectively. Among the 33 long-term progression- ...

4.

pmc.ncbi.nlm.nih.gov

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

Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus ...

These neuroblastoma patients (33 males and 24 females) ranged from 2.4 to 31.3 y of age (median 6.8) at the start of hu3F8 treatment, and 0.6– ...

5.

mycancergenome.org

mycancergenome.org/content/clinical_trials/NCT03033303/

Clinical Trial: NCT03033303 - Neuroblastoma

Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects. Related Conditions: Neuroblastoma ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6016521/

Children's Oncology Group Study ANBL0931 - PMC

A phase 3 randomized study (COG ANBL0032) demonstrated significantly improved outcome by adding immunotherapy with ch14.18 antibody to isotretinoin as post- ...

7.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2703119

Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing ...

This phase 1 clinical trial found hu3F8 to be associated with modest toxic effects, low immunogenicity, and substantial antineuroblastoma activity.