Dinutuximab + Chemotherapy for High-Risk Neuroblastoma

Recruiting at 178 trial locations

Overseen By Timothy C. Griffin

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Bone marrow failure, Primary immunodeficiency, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

478 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding dinutuximab, an antibody that aids the immune system in attacking cancer cells, enhances the effectiveness of standard chemotherapy for children with newly diagnosed high-risk neuroblastoma. Participants will be randomly assigned to receive either standard chemotherapy or a combination of chemotherapy and dinutuximab, followed by surgery. This approach, known as chemoimmunotherapy, could potentially improve outcomes for this aggressive cancer. The study seeks children recently diagnosed with high-risk neuroblastoma, confirmed by specific tumor characteristics. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic immunosuppressive medications for reasons other than certain treatments, you may not be eligible to participate.

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

Research has shown that dinutuximab, a monoclonal antibody, is generally safe for patients with high-risk neuroblastoma. This treatment targets a molecule called GD2 on cancer cells, aiding the immune system in attacking the tumor. In earlier studies, some patients experienced side effects, but these were manageable. The most common side effects included pain and mild allergic reactions, which were usually temporary and treatable with other medications. Since dinutuximab is already used to treat high-risk neuroblastoma, additional evidence supports its safety. While all treatments carry risks, data suggests that dinutuximab is a safe option for many patients. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for neuroblastoma?

Most treatments for high-risk neuroblastoma involve chemotherapy and surgery, but dinutuximab offers something different. Dinutuximab is unique because it targets the GD2 molecule found on neuroblastoma cells, enhancing the immune system's ability to attack these cancer cells. Researchers are excited about this treatment as it represents a more precise approach that could improve outcomes by directly engaging the body's natural defenses. Additionally, combining dinutuximab with chemotherapy might boost the overall effectiveness, offering new hope for better survival rates in children with this aggressive cancer.

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

Research has shown that dinutuximab can help children with high-risk neuroblastoma. One study found that children who received dinutuximab had a 5-year event-free survival (EFS) rate of about 57%, compared to 46% for those who did not receive it. This indicates that children on dinutuximab experienced fewer relapses or complications. Additionally, dinutuximab significantly reduced death rates in patients. The treatment aids the immune system in finding and destroying cancer cells by specifically targeting a molecule called GD2 on the surface of neuroblastoma cells. In this trial, participants in Arm B will receive dinutuximab in combination with chemotherapy during the induction phase. These promising results suggest that dinutuximab could be a valuable addition to chemotherapy for treating high-risk neuroblastoma in children. ^{2 3 5 6 7}

Who Is on the Research Team?

Sara M Federico

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children with high-risk neuroblastoma, a type of cancer. It's open to those under 30 at diagnosis and includes various stages of the disease if certain conditions are met, like specific genetic features or prior limited treatment. Participants need a minimum body surface area and must consent to molecular testing.

Inclusion Criteria

I was diagnosed with a high-risk disease before turning 31.

I haven't had cancer treatment except as allowed in the criteria.

Patients must be enrolled on APEC14B1 and have consented to testing through the Molecular Characterization Initiative (MCI), prior to enrollment on ANBL2131

Exclusion Criteria

I am on long-term immunosuppressive medication for a condition not specified.

All patients and/or their parents or legal guardians must sign a written informed consent

My age, cancer stage, and genetic test results do not match certain criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive chemotherapy and are randomized to receive either standard treatment or chemoimmunotherapy with dinutuximab. This phase includes multiple cycles of chemotherapy and surgery.

5 cycles (approximately 15 weeks)

Multiple visits for chemotherapy administration and surgery

Extended Induction

For patients with poor tumor response, additional cycles of chemoimmunotherapy with dinutuximab, temozolomide, and irinotecan are administered.

Up to 6 cycles (approximately 18 weeks)

Consolidation

Patients undergo two autologous hematopoietic stem cell transplantations and receive high-dose chemotherapy.

Approximately 10-14 weeks

Post-Consolidation

Participants receive dinutuximab and isotretinoin to maintain the response achieved with previous therapy.

5 cycles (approximately 20 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 10 years

Regular follow-up visits at 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months, then periodically

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy
• Dinutuximab
• Stem Cell Transplantation
• Surgery

Trial Overview The study tests dinutuximab added to induction chemotherapy, followed by surgery, radiation therapy, stem cell transplantation, and more chemo. Dinutuximab targets cancer cells for immune destruction; other drugs aim to stop cancer growth or spread.

How Is the Trial Designed?

Group I: Arm B (Dinutuximab in induction) Experimental Treatment 27 Interventions

See detailed description

Group II: Arm A (SOC treatment) Active Control 27 Interventions

See detailed description

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 25 patients with relapsed/refractory neuroblastoma, the combination of dinutuximab beta with chemotherapy regimens N5 and N6 showed an acceptable safety profile, with no unexpected severe toxicities reported.

The treatment resulted in a 48% objective response rate and a 1-year overall survival rate of 44%, indicating promising efficacy in heavily pretreated patients, suggesting the need for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy. Lode, HN., Ladenstein, R., Troschke-Meurer, S., et al.[2023]

Dinutuximab beta (Qarziba®) has been integrated into the standard treatment for high-risk neuroblastoma in Europe, showing positive clinical responses in both first-line and relapsed cases, which has improved patient outcomes.

While effective, dinutuximab beta can cause significant adverse effects such as pain, allergic reactions, and capillary leak syndrome, highlighting the need for optimized management strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Evidence-Based Clinical Guide for the Use of Dinutuximab Beta in Pediatric Patients with Neuroblastoma. Balaguer, J., García Hidalgo, L., Hladun, R., 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 phase 3 trial involving 406 children and young people with high-risk neuroblastoma, the addition of subcutaneous IL-2 to dinutuximab beta did not improve event-free survival rates compared to dinutuximab beta alone, with 3-year event-free survival rates of 60% and 56% respectively.

The combination treatment with subcutaneous IL-2 resulted in significantly higher toxicity, leading to a lower treatment completion rate (62% vs. 87% for dinutuximab beta alone), indicating that dinutuximab beta with isotretinoin should remain the standard care for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Ladenstein, R., Pötschger, U., Valteau-Couanet, D., et al.[2022]

In a study of 25 children with relapsed or refractory high-risk neuroblastoma, combining irinotecan/temozolomide chemotherapy with the anti-GD2 antibody dinutuximab beta resulted in a 64% objective response rate, with 32% achieving complete remission.

The treatment was well tolerated, even in patients who had previously received dinutuximab beta, and no patients discontinued due to toxicities, suggesting it is a promising option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinutuximab beta combined with chemotherapy in patients with relapsed or refractory neuroblastoma. Wieczorek, A., Zaniewska-Tekieli, A., Ehlert, K., et al.[2023]

Dinutuximab is a monoclonal antibody that targets GD2, a glycolipid overexpressed in neuroblastoma, and has been approved by the US FDA for treating high-risk neuroblastoma in children when used in combination with other therapies.

The drug works by inducing immune responses that kill cancer cells, and its development has progressed through multiple phases, with ongoing regulatory reviews in the EU and other countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinutuximab: first global approval. Dhillon, S.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8046731/

Long-term follow-up of a Phase III Study of ch14.18 ... Conclusions: Immunotherapy with dinutuximab improved outcome for patients with high-risk neuroblastoma. Early stoppage for efficacy resulted in a smaller sample ...

2. unituxin.com unituxin.com/hcp/about-unituxin/clinical-trial-data/

Efficacy and Clinical Trial Data 5-year EFS was 57±4.7% for patients randomized to the Unituxin group (n=114) vs 46±5.1% for those randomized to the RA-only group (n=112; P=0.042).4. 5-year EFS ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e22000

Efficacy and safety of dinutuximab in the management ... Conclusions: Our findings suggest that dinutuximab is linked to a significant reduction in overall mortality and a noteworthy improvement in the ...

4. link.springer.com link.springer.com/article/10.1007/s11523-025-01155-3

Efficacy and Safety of Anti-GD2 Immunotherapy with ... Where reported, 3-year OS rates for patients receiving dinutuximab beta were 54–86% overall, with better OS rates reported for refractory than ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210859

GD2-CART01 for Relapsed or Refractory High-Risk ... Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10729685/

Safety and efficacy of dinutuximab in the treatment of ... High-risk NB responds well to monoclonal antibodies (mAbs) that target GD2. However, different anti-GD2 antibodies have various outcomes and side effects.[7] ...

7. authorea.com authorea.com/doi/full/10.22541/au.172505256.69068287/v1

Efficacy and Safety of anti-GD2 monoclonal antibodies in ... High-risk Neuroblastoma (HR-NB) has a poor prognosis despite several treatment strategies. Anti-GD2 monoclonal antibodies (dinutuximab) have ...