Isotretinoin +/- Immunotherapy for Neuroblastoma

Recruiting at 209 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-GD2 antibodies

Disqualifiers: Progressive disease, Veno-occlusive disease, 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: Unknown

Duration: 28 weeks

1449 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This partially randomized phase III trial studies isotretinoin with dinutuximab, aldesleukin, and sargramostim to see how well it works compared to isotretinoin alone following stem cell transplant in treating patients with neuroblastoma. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as dinutuximab, may block tumor growth in different ways by targeting certain cells. Aldesleukin and sargramostim may stimulate a person's white blood cells to kill cancer cells. It is not yet known if chemotherapy is more effective with or without dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating neuroblastoma.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a seizure disorder, you can participate if your condition is well-controlled with anticonvulsants.

What safety data exists for the combination of isotretinoin and immunotherapy in treating neuroblastoma?

The combination of isotretinoin and immunotherapy, including drugs like dinutuximab, IL-2, and GM-CSF, has been used in high-risk neuroblastoma patients, showing improved survival but also significant side effects. Common severe side effects include pain, infections, and fever, with some cases requiring intensive care, but no treatment-related deaths were reported. ^{1 2 3 4 5}

How does the drug isotretinoin differ from other treatments for neuroblastoma?

Isotretinoin, often used in combination with immunotherapy, is unique for neuroblastoma as it acts as a differentiation agent, helping cancer cells mature into normal cells. It is part of the standard care for high-risk neuroblastoma patients, especially after high-dose chemotherapy and stem cell rescue, and has shown to improve survival rates when used in prolonged schedules. ^{1 2 3 5 6}

What data supports the effectiveness of the drug combination of Isotretinoin, Aldesleukin, Dinutuximab, and Sargramostim for treating neuroblastoma?

Research shows that adding immunotherapy with the ch14.18 antibody to isotretinoin significantly improves outcomes for high-risk neuroblastoma patients. Additionally, a study found that combining anti-GD2 immunotherapy with isotretinoin, GM-CSF, and IL-2 improved long-term survival rates for these patients. ^{3 5 6 7 8}

Who Is on the Research Team?

Alice L Yu

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients with high-risk neuroblastoma who have completed intensive induction, stem cell transplant, and radiotherapy. Eligible participants must not have had prior anti-GD2 antibody therapy, should be able to perform daily activities at least half of the time (>=50% performance score), expect to live more than 2 months, and have adequate organ function. They must also agree to use birth control if applicable and cannot be breastfeeding.

Inclusion Criteria

My heart's pumping ability is confirmed to be normal by recent tests.

I have high-risk neuroblastoma, or it became high-risk after initial diagnosis.

I completed therapy for my cancer, including intensive treatment and a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isotretinoin with or without dinutuximab, aldesleukin, and sargramostim following stem cell transplant

28 weeks

Multiple visits for each course

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Aldesleukin
• Dinutuximab
• Isotretinoin
• Sargramostim

Trial Overview The study tests whether adding dinutuximab (a monoclonal antibody), aldesleukin (stimulates white blood cells), and sargramostim (boosts immune system) to isotretinoin chemotherapy improves outcomes in neuroblastoma post-stem cell transplant compared to isotretinoin alone. It's a phase III trial where some patients are randomly chosen to receive the additional drugs.

How Is the Trial Designed?

Group I: Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) Experimental Treatment 7 Interventions

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive immunotherapy comprising sargramostim SC or IV over 2 hours on days 0-13 during courses 1, 3, and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5. Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy.

Group II: Arm I (isotretinoin) (closed to accrual as of 4/16/2009) Active Control 4 Interventions

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive isotretinoin PO BID for 14 days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Safety Trial of Chimeric Antibody 14.18 With GM-CSF, IL-2, and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy: Children's Oncology Group Study ANBL0931. [2019]

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

Prolonged progression-free survival after consolidating second or later remissions of neuroblastoma with Anti-GD2 immunotherapy and isotretinoin: a prospective Phase II study. [2021]

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

Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Practical implications for the administration of 13-cis retinoic acid in pediatric oncology. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-GD2 Based Immunotherapy Prevents Late Events in High-Risk Neuroblastoma Patients over 18 Months at Diagnosis. [2021]

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

Prolonged Isotretinoin in Ultra High-Risk Neuroblastoma. [2018]

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

Targeted isotretinoin in neuroblastoma: kinetics, genetics, or absorption. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment-Related Toxicities During Anti-GD2 Immunotherapy in High-Risk Neuroblastoma Patients. [2021]