Isotretinoin +/- Immunotherapy for Neuroblastoma

Not currently recruiting at 220 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding immunotherapy drugs (dinutuximab, aldesleukin, and sargramostim) to isotretinoin is more effective than using isotretinoin alone for treating neuroblastoma after a stem cell transplant. Isotretinoin targets tumor cells, while the immunotherapy drugs enhance the immune system's ability to attack cancer cells. Individuals with high-risk neuroblastoma who have completed intensive treatment, including a stem cell transplant, and have not received previous anti-disialoganglioside antibody therapy might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Previous studies have safely used isotretinoin to treat neuroblastoma, a type of cancer. The FDA has approved it for other uses, indicating its safety.

Research has shown that sargramostim is generally well-tolerated. It aids in the faster recovery of white blood cells and supports the body in fighting cancer, with a good safety record.

Studies on dinutuximab have reported some serious side effects, such as pain and allergic reactions, but these occur in only a small number of patients.

Aldesleukin, another drug in this trial, is also considered safe and tolerable. Some patients experienced side effects, but they were usually manageable.

Overall, the combination of these treatments has been tested before. While there are some risks, they are known and can be managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for neuroblastoma because they offer innovative approaches to enhancing the immune system's ability to fight cancer. While isotretinoin is already used to induce cancer cell differentiation, combining it with immunotherapy agents like sargramostim, dinutuximab, and aldesleukin in Arm II is a novel approach. This combination aims to supercharge the body's immune response against cancer cells, potentially leading to better outcomes than isotretinoin alone. By targeting cancer cells more aggressively and precisely, these treatments could improve survival rates and offer hope for patients who have limited options.

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

This trial will compare isotretinoin alone with a combination of isotretinoin, dinutuximab, aldesleukin, and sargramostim for treating neuroblastoma. Research has shown that combining isotretinoin with dinutuximab, aldesleukin, and sargramostim can significantly improve outcomes for patients with neuroblastoma. Studies have found that this combination works better than standard treatments. Dinutuximab targets cancer cells to stop their growth. Aldesleukin and sargramostim increase white blood cells, which can attack and destroy cancer cells. Previous research suggests that using these therapies together offers a promising way to treat neuroblastoma. ^{6 7 8 9 10}

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20879881/

Anti-GD2 antibody with GM-CSF, interleukin-2, and ... - PubMed Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00026312

Study Details | NCT00026312 | Isotretinoin With or Without ... 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 ...

3. nejm.org nejm.org/doi/abs/10.1056/NEJMoa0911123

Anti-GD2 Antibody with GM-CSF, Interleukin-2, and ... Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with ...

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

Long-term follow-up of a Phase III Study of ch14.18 ... Patients recieved 6 cycles of isotretinoin with or without 5 cycles of immunotherapy which consists of dinutuximab with GM-CSF alternating with IL2. Accrual was ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01630

Anti-GD2 Antibody Dinutuximab Beta and Low-Dose ... Survival rates for patients with relapsed high-risk neuroblastoma are poor. This study examined feasibility, safety, and response to an ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7772209/

Impact of IL-2 on Treatment Tolerance in Patients With High ... No evidence was found that addition of IL-2 to DB given as an 8-h short-term infusion improved outcomes in patients with high-risk neuroblastoma ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31358541/

Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF ... Hu14.18-IL2 given in combination with GM-CSF and isotretinoin is safe and tolerable. Patients with MIBG and/or bone marrow-only disease had a 16.1% response ...

8. aetna.com aetna.com/cpb/medical/data/1_99/0024.html

Aldesleukin (Proleukin) - Medical Clinical Policy Bulletins Aetna considers continuation of aldesleukin (Proleukin) therapy medically necessary for neuroblastoma ... This study evaluated the safety and effectiveness of IL- ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/12/6/1750/285125/A-Phase-I-Clinical-Trial-of-the-hu14-18-IL2-EMD

A Phase I Clinical Trial of the hu14.18-IL2 (EMD 273063) as a ... Purpose: Evaluate the clinical safety, toxicity, immune activation/modulation, and maximal tolerated dose of hu14.18-IL2 (EMD 273063) in pediatric patients ...

10. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)47691-6/fulltext

Feasibility of high-dose interleukin-2 in heavily pretreated ... Safety and toxicity profile. Eight patients completed all five cycles of IL-2 therapy. In two patients treatment had to be stopped as a result of toxicity. One ...