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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N10 chemotherapy is safe and effective for children with high-risk neuroblastoma, a cancer that usually affects young kids. Participants will receive chemotherapy alongside a monoclonal antibody treatment called DANYELZA (naxitamab-gqgk). The study seeks children under 19 diagnosed with neuroblastoma, particularly those with a rapidly spreading form. It suits those who have undergone only one round of treatment and are ready to try something new. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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 N10 chemotherapy is likely to be safe for children with high-risk neuroblastoma?

Research has shown that DANYELZA, the treatment under study in this trial, has undergone safety testing in previous studies. Many patients have responded well, with more than one-third showing positive results and over one-fourth experiencing a complete response.

However, serious reactions have been reported during DANYELZA infusions, including severe heart problems and anaphylaxis. Despite these risks, many patients generally tolerate the treatment well.

This study is in Phase 2, indicating that the treatment has already passed some initial safety tests. This phase aims to further assess its safety and effectiveness in a larger group of patients. Prospective participants should consider these points to weigh the potential benefits and risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about DANYELZA for treating neuroblastoma because it works differently than current standard treatments like chemotherapy and radiation. DANYELZA uses a monoclonal antibody that specifically targets cancer cells, potentially offering a more precise attack on the tumor with fewer side effects. This targeted approach could improve outcomes by reducing the need for high doses of traditional chemotherapy, which often comes with significant side effects. By focusing on the unique markers on neuroblastoma cells, DANYELZA provides a new mechanism of action, offering hope for more effective and less toxic treatment options.

What evidence suggests that DANYELZA might be an effective treatment for neuroblastoma?

Research has shown that DANYELZA, also known as naxitamab, holds promise for treating high-risk neuroblastoma, a type of cancer. In one study, more than a third of patients had a positive response, and over a quarter experienced a complete response, meaning their cancer was no longer detectable. Another study found that 68% of patients responded well, with 59% achieving full remission, where the cancer disappeared. Additionally, some patients had a 5-year event-free survival rate of nearly 58%, meaning they had no cancer-related issues for five years, and an overall survival rate of about 79%. These results suggest that DANYELZA could be an effective option for those battling this aggressive cancer. Participants in this trial will receive DANYELZA as part of a treatment regimen for neuroblastoma. ^{1 4 5 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 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

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

I have been diagnosed with neuroblastoma based on tests.

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

Exclusion Criteria

Inability to comply with protocol requirements

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

Pregnancy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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]

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 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]

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]

Citations

1. danyelzahcp.com danyelzahcp.com/efficacy/study-results/

Efficacy: Study Results | DANYELZA® (naxitamab-gqgk) In the DANYELZA Studies 12-230 and 201 initial analysis, more than 1/3 of patients responded and more than 1/4 achieved a complete response.

2. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-naxitamab-high-risk-neuroblastoma-bone-or-bone-marrow

FDA grants accelerated approval to naxitamab for high-risk ... The main efficacy outcome measures were confirmed overall response rate (ORR) per the revised International Neuroblastoma Response Criteria ( ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03363373

NCT03363373 | Naxitamab for High-Risk Neuroblastoma ... A pivotal phase 2 trial of antibody Naxitamab (hu3F8) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in high-risk neuroblastoma patients.

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)43076-5/fulltext

75P Efficacy and updated safety results from pivotal phase ... By independent review, the overall response rate (ORR) was 68% (15/22) with 59% (13/22) complete responses (CR). In refractory pts the ORR was 71% (10/14) with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10177429/

Naxitamab Combined with Granulocyte-Macrophage Colony ... The results demonstrate reassuring survival rates (5-year event-free survival of 57.9% and overall survival of 78.6%) for high-risk neuroblastoma patients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03363373

Study Details | NCT03363373 | Naxitamab for High-Risk ... Children and adults diagnosed with high-risk neuroblastoma patients with primary refractory disease or incomplete response to salvage treatment in bone ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761171lbl.pdf

DANYELZA (naxitamab-gqgk) Label - accessdata.fda.gov Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis,.