MIBG + Dinutuximab Therapy for Neuroblastoma

Recruiting at 11 trial locations

Overseen By Araz Marachelian, MD, MS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: New Approaches to Neuroblastoma Therapy Consortium

Must not be taking: QTc prolonging, Valproic acid

Disqualifiers: Pregnancy, Organ transplant, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of a radioactive drug, an antibody, and possibly another drug in children with hard-to-treat neuroblastoma. The treatment works by killing cancer cells directly and helping the immune system attack them.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications that interfere with MIBG uptake, prolong QTc, or include valproic acid (for Part B) are not allowed. It's best to discuss your current medications with the study team.

Is MIBG + Dinutuximab therapy safe for treating neuroblastoma?

131I-MIBG therapy has been used in treating neuroblastoma, and while it can be effective, there are safety concerns such as the risk of developing secondary leukemia. However, some studies have shown that it can be used without significant blood-related side effects, especially when used at lower doses. ^{1 2 3 4 5}

What makes MIBG + Dinutuximab therapy unique for treating neuroblastoma?

MIBG + Dinutuximab therapy is unique because it combines a targeted radioactive treatment (MIBG) with an immunotherapy (Dinutuximab) that specifically targets neuroblastoma cells, potentially enhancing the effectiveness of treatment while reducing toxicity compared to traditional chemotherapy. ^{3 4 6 7 8}

What data supports the effectiveness of the MIBG + Dinutuximab treatment for neuroblastoma?

Research shows that 131-I-MIBG, a component of the treatment, has been effective in reducing tumor size in neuroblastoma patients, with some achieving complete or partial responses. It is considered an active treatment option, especially for advanced or relapsed cases, and is comparable to chemotherapy in efficacy with less toxicity. ^{1 3 5 9 10}

Who Is on the Research Team?

Thomas Cash, MD

Principal Investigator

Children's Healthcare of Atlanta

Araz Marachelian, MD, MS

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for pediatric patients with high-risk neuroblastoma, a type of cancer. They must have evidence of MIBG uptake in tumors or increased urinary catecholamines and meet specific criteria regarding their disease state (recurrent/progressive, refractory, persistent). Participants need to be recovered from prior treatments and have adequate organ function. Pregnant individuals or those unable to follow the study plan are excluded.

Inclusion Criteria

My cancer shows MIBG uptake in at least one site, confirmed within the last 28 days.

I have been diagnosed with neuroblastoma confirmed by tests.

My neuroblastoma is classified as high-risk according to COG.

Exclusion Criteria

I am currently receiving hemodialysis.

I have chosen not to participate in the NANT 2004-05 study.

I have had anti-GD2 therapy but not with 131I-MIBG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 131I-MIBG, dinutuximab, and GM-CSF, with optional vorinostat in Cohort B

8 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 months

What Are the Treatments Tested in This Trial?

Interventions

• 131I-MIBG
• Dinutuximab
• Vorinostat

Trial Overview The trial tests a combination therapy using 131I-MIBG with dinutuximab for children with neuroblastoma that's resistant or has come back after treatment. If safe, vorinostat will be added at a certain dose level. The study uses a 'rolling 6' design to find the best dose for phase 2 trials and includes additional patient groups to confirm findings.

How Is the Trial Designed?

Group I: Cohort B DL4 Experimental Treatment 5 Interventions

Vorinostat will be given on days 0-13 at 180 mg/m2/dose. Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group II: Cohort A DL3 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group III: Cohort A DL2 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 15 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

Group IV: Cohort A DL1 Experimental Treatment 4 Interventions

Patients will receive 131I-MIBG on day 1 at 12 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy

131I-MIBG is already approved in United States, European Union for the following indications:

Approved in United States as Azedra for:

• Pheochromocytoma
• Neuroblastoma

Approved in European Union as Iobenguane I-131 for:

• Neuroblastoma
• Pheochromocytoma
• Paraganglioma

Who Is Running the Clinical Trial?

New Approaches to Neuroblastoma Therapy Consortium

Lead Sponsor

Trials

19

Recruited

1,700+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

United Therapeutics

Industry Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

In a pilot study involving 68 children with newly diagnosed high-risk neuroblastoma, 86.8% completed induction chemotherapy and received 131 I-MIBG therapy, demonstrating the treatment's feasibility.

The study found that while there were some severe side effects, including sinusoidal obstruction syndrome (SOS), the 15 mCi/kg dose of 131 I-MIBG showed a high feasibility rate of 96.7%, supporting further investigation in a larger randomized trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Weiss, BD., Yanik, G., Naranjo, A., et al.[2022]

The study involving 32 newly diagnosed stage 4 neuroblastoma patients demonstrated that upfront treatment with 131I-MIBG is feasible and can be administered within 2 weeks of diagnosis, with a response rate of 38% after this therapy.

Following myeloablative therapy and autologous stem cell rescue, the overall response rate for patients who received 131I-MIBG was 71%, significantly higher than the 36% response rate in the chemotherapy group, indicating that 131I-MIBG is an effective option in the treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients. Kraal, KC., Bleeker, GM., van Eck-Smit, BL., et al.[2017]

(131)I-meta iodobenzylguanidine ((131)I-mIBG) is an active treatment for neuroblastoma, showing a variable objective tumor response rate of 0% to 75% across 25 studies, with a mean response of 32%.

Despite its activity, the optimal use and effectiveness of (131)I-mIBG remain unclear due to the lack of randomized controlled trials and significant heterogeneity in study designs, highlighting the need for more rigorous prospective trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. Wilson, JS., Gains, JE., Moroz, V., et al.[2022]

A study involving 24 high-risk neuroblastoma patients showed that using 131I-mIBG as part of the treatment regimen is feasible and tolerable, especially when combined with myeloablative chemotherapy and hematopoietic stem cell transplantation.

The treatment resulted in improved outcomes for patients who had a partial response before receiving 131I-mIBG, with some achieving complete or very good partial responses, highlighting the potential effectiveness of this approach in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront consolidation treatment with 131I-mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma. Feng, J., Cheng, FW., Leung, AW., et al.[2022]

In a study of 111 stage 4 neuroblastoma patients, those who received (131)I-MIBG therapy showed better 3-year event-free survival (46%) and overall survival (58%) compared to those who did not receive the therapy (19% and 43%, respectively).

However, when analyzing patients who underwent high-dose chemotherapy with autologous stem cell transplantation, the outcomes were similar regardless of (131)I-MIBG therapy, indicating that the benefits of (131)I-MIBG may be overshadowed by the effects of ASCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. Schmidt, M., Simon, T., Hero, B., et al.[2022]

Citations

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

Critical observations on neuroblastoma treatment with 131-I-metaiodobenzylguanidine at diagnosis. [2019]

2. England pubmed.ncbi.nlm.nih.gov

First line targeted radiotherapy, a new concept in the treatment of advanced stage neuroblastoma. [2019]

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

A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Feasibility, toxicity and response of upfront metaiodobenzylguanidine therapy therapy followed by German Pediatric Oncology Group Neuroblastoma 2004 protocol in newly diagnosed stage 4 neuroblastoma patients. [2017]

5. England pubmed.ncbi.nlm.nih.gov

A systematic review of 131I-meta iodobenzylguanidine molecular radiotherapy for neuroblastoma. [2022]

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

Secondary myelodysplastic syndrome and leukemia following 131I-metaiodobenzylguanidine therapy for relapsed neuroblastoma. [2019]

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

Phase II study of 131 I-metaiodobenzylguanidine with 5&#160;days of topotecan for refractory or relapsed neuroblastoma: Results of the French study MIITOP. [2023]

8. Italy pubmed.ncbi.nlm.nih.gov

Nuclear medicine therapy of neuroblastoma. [2013]

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

Upfront consolidation treatment with 131I-mIbG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004. [2022]