Chemoimmunotherapy for Neuroblastoma

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Severe organ dysfunction, Low ANC, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to treat neuroblastoma, a type of cancer that mostly affects children. Researchers aim to determine if the experimental drug Hu3F8, combined with chemotherapy drugs irinotecan and temozolomide, and another drug called GM-CSF (a type of growth factor), is safe and effective. Potential participants include those diagnosed with high-risk neuroblastoma who have had limited success with previous treatments. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, prior treatment with certain drugs like irinotecan or temozolomide is allowed, suggesting that some medications may be continued. It's best to discuss your specific medications with the trial coordinators.

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

Research has shown that the combination of the experimental drug Hu3F8 with chemotherapy drugs irinotecan and temozolomide, plus GM-CSF, has been studied before. These studies focused on patient tolerance to the treatment.

Reports indicate that similar drug combinations, such as irinotecan and temozolomide with other drugs, have been safely used in children with neuroblastoma, generally resulting in mild side effects. However, since Hu3F8 remains experimental, additional safety information is necessary.

As this trial is in an early stage, researchers are closely monitoring the treatment to better understand its safety in humans. Previous studies suggest it might be safe, but more evidence is needed for this specific combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the chemoimmunotherapy treatment for neuroblastoma because it combines the power of targeted immunotherapy with traditional chemotherapy. Unlike standard treatments like surgery, radiation, and chemotherapy alone, this approach uses Hu3F8, a monoclonal antibody, to direct the immune system specifically against neuroblastoma cells. Additionally, it incorporates Sargramostim (GM-CSF) to boost the immune response, alongside Irinotecan and Temozolomide, which are established chemotherapy agents. This combination aims to improve effectiveness by attacking the cancer on multiple fronts, potentially leading to better outcomes for patients.

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

This trial will evaluate the combination of Hu3F8, Irinotecan, Temozolomide, and GM-CSF, known as the HITS regimen, for treating neuroblastoma. Studies have shown that Hu3F8, a specially designed protein, can effectively target neuroblastoma cells. In one trial, Hu3F8 combined with GM-CSF, which aids the immune system, showed promising results for treating neuroblastoma with manageable side effects. Irinotecan, a chemotherapy drug, has completely shrunk tumors in several studies. Temozolomide, another chemotherapy drug, has shown effectiveness in neuroblastoma patients, especially when paired with irinotecan. Together, these drugs aim to form a powerful combination to fight neuroblastoma by attacking cancer cells and boosting the immune system. ^{1 6 7 8 9}

Who Is on the Research Team?

Shakeel Modak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for children and adults with high-risk neuroblastoma, a type of cancer. Participants must have specific stages of the disease, measurable or evaluable disease after prior therapy, and cannot be in complete remission. They can't join if they have severe organ damage, low blood counts, allergies to mouse proteins, active infections or are pregnant/breastfeeding.

Inclusion Criteria

My neuroblastoma is considered high-risk based on its stage and genetic features.

My neuroblastoma diagnosis is confirmed by tissue tests or bone marrow and urine tests.

I have had specific previous treatments under certain conditions.

Exclusion Criteria

My major organs are functioning well, with no severe issues.

I do not have a severe infection that is threatening my life.

ANC < 500/uL

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Hu3F8, irinotecan, temozolomide, and GM-CSF in cycles. Each cycle consists of four doses of Hu3F8, five doses each of irinotecan and temozolomide, and five doses of GM-CSF.

4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• GM-CSF
• Hu3F8
• Irinotecan
• Temozolomide

Trial Overview The study tests an experimental drug called Hu3F8 combined with chemotherapy drugs irinotecan and temozolomide plus GM-CSF to see if this mix is safe and effective against neuroblastoma.

How Is the Trial Designed?

Group I: Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Experimental Treatment 4 Interventions

Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Y-mAbs Therapeutics

Industry Sponsor

Trials

26

Recruited

1,600+

Y-Mabs, Inc

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

In a phase I trial involving 14 children with recurrent high-risk neuroblastoma, an all-oral regimen of irinotecan and temozolomide was found to be feasible and well tolerated, with 50% of patients showing a response or disease stabilization for three or more treatment courses.

The maximum-tolerated dose (MTD) was established at 60 mg/m2/d for oral irinotecan combined with 75 mg/m2/d of temozolomide, demonstrating similar plasma exposure levels to those seen with intravenous irinotecan, suggesting this oral combination could be a viable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of oral irinotecan and temozolomide for children with relapsed high-risk neuroblastoma: a new approach to neuroblastoma therapy consortium study. Wagner, LM., Villablanca, JG., Stewart, CF., et al.[2021]

In a phase II study involving 55 children with relapsed/refractory neuroblastoma, the combination of irinotecan and temozolomide showed an objective response rate of 15%, indicating potential efficacy, especially in patients whose disease was assessable by MIBG or bone marrow analysis.

The treatment was well tolerated, with less than 6% of patients experiencing severe diarrhea and less than 10% developing infections during neutropenia, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan and temozolomide in children with relapsed or refractory neuroblastoma: a Children's Oncology Group study. Bagatell, R., London, WB., Wagner, LM., et al.[2022]

The combination treatment of irinotecan, temozolomide, dintuximab, and GM-CSF (I/T/DIN/GM-CSF) showed significant antitumor activity in patients with relapsed or refractory neuroblastoma, with an overall objective response rate of 41.5% across 53 patients.

The treatment was associated with a one-year progression-free survival rate of 67.9% and an overall survival rate of 84.9%, although it also resulted in notable grade ≥ 3 toxicities, including fever/infection and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. Mody, R., Yu, AL., Naranjo, A., et al.[2021]

In a phase 2 trial involving patients with high-risk neuroblastoma, the combination of irinotecan, temozolomide, and immunotherapy (dinutuximab and GM-CSF) showed a response rate of 53% in the initial cohort, indicating its potential efficacy for treating relapsed or refractory cases.

The study found that specific genotypes related to natural killer (NK) cell activity, particularly KIR and their ligands, were associated with clinical outcomes, highlighting the importance of genetic factors in the effectiveness of the chemoimmunotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KIR/KIR-ligand genotypes and clinical outcomes following chemoimmunotherapy in patients with relapsed or refractory neuroblastoma: a report from the Children's Oncology Group. Erbe, AK., Diccianni, MB., Mody, R., et al.[2023]

In a study involving 35 children with relapsed or refractory neuroblastoma, the combination of irinotecan, temozolomide, and dinutuximab showed significant anti-tumor activity, with 53% of patients achieving an objective response, including complete responses.

In contrast, the combination of irinotecan, temozolomide, and temsirolimus had a much lower response rate, with only 6% of patients showing a partial response, indicating that the dinutuximab combination is more promising for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Mody, R., Naranjo, A., Van Ryn, C., et al.[2022]

The combination of vincristine, irinotecan, and temozolomide (VIT) was found to be an effective treatment for relapsed or refractory neuroblastoma, achieving an overall objective response rate of 69.6% in a study of 46 patients.

The VIT regimen was well-tolerated, with most toxicities being manageable; while some patients experienced Grade 3-4 hematologic toxicity, the regimen was still considered active and safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma. Zhu, J., Wang, J., Sun, F., et al.[2022]

In a Phase I trial involving three children with advanced neuroblastoma, the maximum tolerated dose (MTD) of irinotecan hydrochloride (CPT-11) was determined to be 180 mg/m2 administered over three days, with manageable myelosuppression as a side effect.

The treatment showed promising efficacy, with one child achieving a complete response and two others showing partial responses, suggesting that CPT-11 could be a valuable option for treating this type of cancer, warranting further research into its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase I study with irinotecan hydrochloride (CPT-11) for advanced neuroblastoma]. Hirota, T., Kawai, N., Kitagawa, S., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8416151/

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic ... Sargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery ...

2. partnertx.com partnertx.com/comprehensive-review-highlights-importance-of-leukine-in-combination-with-anti-gd2-immunotherapy-for-treatment-of-high-risk-pediatric-neuroblastoma/

Comprehensive Review Highlights Importance of Leukine ... The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs.

3. nature.com nature.com/articles/s41467-025-56619-x

The anti-GD2 monoclonal antibody naxitamab plus GM ... Naxitamab demonstrated clinically meaningful efficacy with manageable safety in patients with residual neuroblastoma in bone/BM.

4. prnewswire.com prnewswire.com/news-releases/comprehensive-review-highlights-importance-of-leukine-in-combination-with-anti-gd2-immunotherapy-for-treatment-of-high-risk-pediatric-neuroblastoma-302037532.html

Comprehensive Review Highlights Importance of Leukine ... The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01757626

NCT01757626 | Combination Therapy of Antibody Hu3F8 ... The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10571514/

Early Salvage Chemo-Immunotherapy with Irinotecan, ... Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03189706/

Clinical Trial: NCT03189706 - Neuroblastoma The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and ...

8. withpower.com withpower.com/trial/early-phase-1-neuroblastoma-5-2017-8a2c5

Chemoimmunotherapy for Neuroblastoma The combination of irinotecan, temozolomide, dinutuximab, and GM-CSF has been studied in children with neuroblastoma, showing an acceptable safety profile. Some ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.10025

Naxitamab-based chemoimmunotherapy for resistant high- ... High-dose naxitamab-based chemoimmunotherapy is safe and effective against chemoresistant HR-NB. This ongoing phase II study may define a broader role for ...