Nivolumab + Dinutuximab for Neuroblastoma

(MiniVan Trial)

Not currently recruiting at 2 trial locations
DP
Overseen ByDanny Pratt
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: University Hospital Southampton NHS Foundation Trust
Stay on Your Current MedsYou can continue your current medications while participating
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for children with neuroblastoma, a challenging cancer that often affects kids. Researchers aim to determine if adding two new medicines, Nivolumab (also known as Opdivo, an immunotherapy drug) and Dinutuximab Beta Antibodies, to a standard treatment can safely enhance the immune system to fight the cancer more effectively. The trial consists of three stages, each testing different combinations and doses of these drugs to ensure safety and effectiveness. Children whose neuroblastoma has returned or not responded to other treatments might be suitable candidates for this trial, especially if their disease appears on a specific type of imaging test. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are taking systemic corticosteroids or other immunosuppressive agents within 14 days before the study.

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

Research has shown that Nivolumab and Dinutuximab Beta have been tested for safety in children with high-risk neuroblastoma. These studies found the combination to be generally well-tolerated. A small study noted that most side effects were manageable and similar to those from other neuroblastoma treatments. Common issues included fever and pain, but these were not severe for most participants.

Nivolumab is already approved for other conditions and is known to be safe for humans. Dinutuximab Beta, used for neuroblastoma, has demonstrated a good safety record when combined with chemotherapy. This suggests that the treatment combination in this trial should be safe for most patients.

Although this trial is in the early stages, with a primary focus on testing safety, existing evidence from other studies is encouraging. Participants will be closely monitored for any side effects to ensure their safety throughout the trial.12345

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for neuroblastoma, which often include chemotherapy and radiation, the combination of Nivolumab and Dinutuximab offers a novel approach by harnessing the immune system. Nivolumab is a checkpoint inhibitor that helps to unmask cancer cells, allowing the immune system to attack them more effectively. Dinutuximab is an antibody that specifically targets neuroblastoma cells, potentially leading to improved recognition and destruction by the immune system. This dual-action strategy could enhance the body's natural defenses against cancer, offering hope for more effective and targeted treatment options.

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

Research has shown that combining nivolumab and dinutuximab beta yields promising results for treating neuroblastoma, particularly when the cancer returns or continues to grow after treatment. In this trial, participants will receive various combinations of these treatments. In some cases, this combination has led to complete remission (where the cancer disappears) or a very good partial remission (where the cancer shrinks significantly) in patients with relapsed or hard-to-treat neuroblastoma. Dinutuximab beta targets cancer cells as an antibody, while nivolumab boosts the immune system's ability to fight cancer. Together, they appear to improve survival rates. These findings offer hope for children facing this challenging disease.678910

Who Is on the Research Team?

JG

Juliet Gray

Principal Investigator

Consultant Paediatric Oncologist

Are You a Good Fit for This Trial?

This trial is for children with relapsed/refractory high-risk neuroblastoma. They must have a certain type of active disease visible on imaging, be past specific treatments like myeloablative chemotherapy, and meet health criteria such as adequate organ function and performance status. Children with severe prior reactions to similar therapies or certain medical conditions are excluded.

Inclusion Criteria

MIBG avid disease on imaging within 4 weeks to study entry.
≥ 3 months since any myeloablative chemotherapy / stem cell rescue
≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy.
See 20 more

Exclusion Criteria

Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody (HACA) (≥ 10 μg/ml)
Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study
You have symptoms of heart failure or an irregular heartbeat that is not under control.
See 12 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cohort 1 Treatment

Patients receive 131-I MIBG and Nivolumab to assess safety and tolerability

12 weeks

Cohort 2 Treatment

Patients receive 131-I MIBG, Nivolumab, and anti-GD2 to assess safety and tolerability

12 weeks

Cohort 3 Treatment

Patients receive full dose of 131-I MIBG, Nivolumab, and anti-GD2 for expanded safety analysis

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • 131-I mIBG
  • Dinutuximab Beta Antibodies
  • Nivolumab
Trial Overview The study tests the safety and potential effectiveness of combining an anti-GD2 antibody (standard treatment) with two drugs: 131-I mIBG (a radioactive compound) and Nivolumab (an immune system-boosting drug). It's an adaptive trial in three cohorts, gradually increasing doses if safe, across hospitals in the UK, Germany, and USA.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

University Hospital Southampton NHS Foundation Trust

Lead Sponsor

Trials
221
Recruited
411,000+

University College London Hospitals

Collaborator

Trials
204
Recruited
1,221,000+

University of Wisconsin, Madison

Collaborator

Trials
1,249
Recruited
3,255,000+

University Hospital Greifswald

Collaborator

Trials
5
Recruited
3,900+

Solving Kids' Cancer US/EU

Collaborator

Trials
2
Recruited
110+

Joining Against Cancer in Kids

Collaborator

Trials
1
Recruited
40+

The Band of Parents

Collaborator

Trials
2
Recruited
110+

Published Research Related to This Trial

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.
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 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.
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]

Citations

Nivolumab and dinutuximab beta in two patients with ...The combination of DB with the checkpoint inhibitor nivolumab led to complete and a very good partial remission in two patients with relapsed/refractory NB.
NCT02914405 | Phase I Study of 131-I mIBG Followed by ...A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. In this research the anti-GD2 ...
3.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/32414861/
Nivolumab and dinutuximab beta in two patients with ...The combination of DB with the checkpoint inhibitor nivolumab led to complete and a very good partial remission in two patients with relapsed/refractory NB.
A study of mIBG, nivolumab and dinutuximab beta for ...This study is looking at combining mIBG, nivolumab and dinutuximab beta to treat neuroblastoma that has continued to grow or came back after treatment.
(PDF) Nivolumab and dinutuximab beta in two patients with ...In these patients, event-free and overall survival was improved by the addition of the anti-disialoganglioside antibody dinutuximab beta (DB) ...
NCT02914405 | Phase I Study of 131-I mIBG Followed by ...A Phase I Study of 131-1 MIBG Followed by Nivolumab and Dinutuximab Beta in Children with Relapsed/refractory Neuroblastoma
Single-Center Cohort of Pediatric Patients with High-Risk ...We report a retrospective study on a small institutional cohort of high-risk neuroblastoma patients treated with Dinutuximab beta and Nivolumab in relapsed or ...
Nivolumab and dinutuximab beta in two patients with ...The presence of MYCN amplification and/or metastatic disease (stage M) are considered high-risk features in patients with NB. In this group, 5- ...
Anti-GD2 Antibody Dinutuximab Beta and Low-Dose ...Patients with high-risk neuroblastoma (HR-NB) have 5-year survival rates of approximately 50%, whereas patients with metastatic disease at ...
Dinutuximab beta plus conventional chemotherapy for ...The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy ...
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