Reduced Chemotherapy and Monoclonal Antibody Therapy for Neuroblastoma

Overseen By Fiorella Iglasias Cardenas, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Severe organ dysfunction, Pregnancy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out whether N10 chemotherapy is a safe and effective treatment for children with high-risk neuroblastoma.

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 DANYELZA (naxitamab) for treating neuroblastoma?

Naxitamab, marketed as DANYELZA, has been approved by the FDA for treating high-risk neuroblastoma in patients who have relapsed or have not responded to other treatments. It has shown effectiveness in combination with another drug, granulocyte-macrophage colony-stimulating factor, in improving outcomes for these patients. ^{1 2 3 4 5}

Is naxitamab safe for use in humans?

Naxitamab, used for treating neuroblastoma, has been shown to be generally safe in humans, with common side effects like pain, rash, and cough being manageable. Serious side effects like capillary leak syndrome and long-term toxicities were not observed in studies, and the treatment is often administered in outpatient settings. ^{1 2 4 6 7}

What makes the drug DANYELZA unique for treating neuroblastoma?

DANYELZA (naxitamab) is unique because it is a humanized monoclonal antibody that specifically targets the GD2 receptor on neuroblastoma cells, and it can be administered on an outpatient basis, making it more convenient for patients. It is particularly used for high-risk neuroblastoma that has relapsed or is resistant to other treatments, offering a new option for these challenging cases. ^{1 3 5 8 9}

Research Team

Brian Kushner, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for children with high-risk neuroblastoma. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may need parental consent.

Inclusion Criteria

I have been diagnosed with neuroblastoma based on tests.

Signed informed consent indicating awareness of the investigational nature of this treatment

My cancer is a specific type of neuroblastoma with certain genetic features.

Exclusion Criteria

I do not have severe problems with my kidneys, heart, liver, brain, lungs, blood, or stomach.

Inability to comply with protocol requirements

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Participants receive 4 cycles of induction chemotherapy

12 weeks

Monoclonal Antibody-Based Therapy

Participants receive 2 cycles of mAb-based therapy to assess response

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• DANYELZA

Trial Overview The study tests N10 chemotherapy's safety and effectiveness in treating high-risk neuroblastoma in children. It involves a combination of drugs: DANYELZA, Sargramostim, Carboplatin, Irinotecan, Temozolomide, Topotecan, Doxorubicin, Cytoxan (Cyclophosphamide), Ifosfamide, Vincristine and Etoposide.

Participant Groups

Group I: Participants with Neuroblastoma Experimental Treatment 11 Interventions

Participants will receive 4 cycles of induction chemotherapy followed by a response-based intervention.

DANYELZA is already approved in United States for the following indications:

Approved in United States as DANYELZA for:

• High-risk neuroblastoma in the bone or bone marrow that has come back (relapsed) or that did not respond to previous treatment (refractory), and has shown a partial response, minor response, or stable disease to prior therapy

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Naxitamab, a monoclonal antibody for treating high-risk neuroblastoma, has a safety profile where over 50% of pediatric patients experienced manageable adverse events like pain, hypotension, and bronchospasm, with some severe cases requiring careful monitoring.

The study emphasizes the importance of premedication and supportive therapies to manage these adverse events effectively, allowing patients to continue treatment and maximize the benefits of naxitamab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. Mora, J., Chan, GC., Morgenstern, DA., et al.[2023]

Naxitamab is a humanized monoclonal antibody specifically designed to target GD2-positive cancers, including neuroblastoma and osteosarcoma, and has received accelerated approval from the US FDA for treating high-risk neuroblastoma in pediatric and adult patients.

The approval allows naxitamab to be used in combination with granulocyte-macrophage colony-stimulating factor for patients who have shown a partial or minor response, or stable disease after previous treatments, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. Markham, A.[2021]

In a study of 34 patients with stage 4 neuroblastoma, treatment with the anti-G(D2) monoclonal antibody 3F8 after chemotherapy led to long-term remission in 13 patients, with no late neurologic complications observed.

The treatment was associated with manageable acute side effects, and a better survival rate was linked to either a transient anti-mouse response or completing four cycles of 3F8, suggesting its potential as a consolidating therapy for high-risk neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. Cheung, NK., Kushner, BH., Cheung, IY., et al.[2020]

In a study of 73 high-risk neuroblastoma patients in complete remission, treatment with naxitamab and GM-CSF resulted in a three-year overall survival rate of 82.4% and an event-free survival rate of 58.4%.

The treatment was generally well-tolerated, with only 5% of patients experiencing severe grade 4 toxicities, and the majority (79.5%) completed the therapy, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. Mora, J., Castañeda, A., Gorostegui, M., et al.[2022]

In a study involving seven patients with high-risk neuroblastoma, dinutuximab treatment led to complete remission in two patients and partial response in three, highlighting its potential effectiveness in eradicating minimal residual disease.

While dinutuximab shows promise as a first-line treatment for high-risk neuroblastoma, it carries a significant risk of severe adverse reactions, necessitating administration by experienced pediatric oncology centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of immunotherapy into the treatment of neuroblastoma - single center experience with the administration of dinutuximab and management of its adverse effects. Achbergerová, M., Hederová, S., Mikesková, M., et al.[2021]

In a study of 34 patients with high-risk neuroblastoma who did not respond completely to initial therapy, the combination of naxitamab, irinotecan, temozolomide, and GM-CSF showed a complete response rate of 29% and a significant improvement in overall survival (OS) and event-free survival (EFS) when treatment was started early.

Patients receiving early treatment (cohort 1) had a 3-year OS of 84.8% and EFS of 54.4%, which were significantly better than those in the late treatment group (cohort 2), highlighting the importance of timing in administering this chemo-immunotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. Muñoz, JP., Larrosa, C., Chamorro, S., et al.[2023]

In a study of 33 infants with high-risk neuroblastoma, anti-GD2 monoclonal antibodies (3F8 and naxitamab) were administered safely during or immediately after chemotherapy, with manageable side effects and no severe long-term toxicities reported.

The treatment showed promising long-term outcomes, with 17 out of 21 patients receiving 3F8 in complete remission after a median of 13.4 years, and 10 out of 12 naxitamab patients remaining relapse-free after a median of 3.1 years, indicating that high-risk neuroblastoma in infants can be highly curable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. Kushner, BH., Modak, S., Kramer, K., et al.[2022]

In a phase II clinical trial involving 64 children with high-risk neuroblastoma, the addition of the monoclonal antibody hu14.18K322A to induction chemotherapy led to a significant early response, with 66.7% of patients showing partial responses or better after the first two cycles.

The treatment was well tolerated and resulted in a median tumor volume reduction of 75%, with a promising 3-year event-free survival rate of 73.7% and overall survival rate of 86%, suggesting that this approach could potentially change treatment practices if confirmed in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. Furman, WL., McCarville, B., Shulkin, BL., et al.[2023]

In a study of 169 children with stage 4 neuroblastoma, the combination of anti-GD2 monoclonal antibody 3F8 with GM-CSF and 13-cis-retinoic acid significantly improved progression-free survival (PFS) and overall survival (OS) rates compared to 3F8 alone, with 5-year OS rates of 81% for the most effective regimen.

The presence of minimal residual disease (MRD) after treatment was identified as a negative prognostic factor, while the absence of certain immune response markers and the use of the most effective treatment regimen (regimen C) were associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. Cheung, NK., Cheung, IY., Kushner, BH., et al.[2021]

References

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

Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and/or relapsed high-risk neuroblastoma: Management of adverse events. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Naxitamab: First Approval. [2021]

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

Anti-G(D2) antibody treatment of minimal residual stage 4 neuroblastoma diagnosed at more than 1 year of age. [2020]

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

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission. [2022]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

Implementation of immunotherapy into the treatment of neuroblastoma - single center experience with the administration of dinutuximab and management of its adverse effects. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes. [2023]

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

Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma. [2022]

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

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. [2023]

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

Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte-macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission. [2021]