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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

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 another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.

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.

What data supports the effectiveness of the chemoimmunotherapy treatment for neuroblastoma?

Research shows that the combination of irinotecan, temozolomide, and GM-CSF (a protein that helps boost the immune system) has shown activity in patients with relapsed or hard-to-treat neuroblastoma, with a response rate of 53% in one study. ^{1 2 3 4 5}

Is the chemoimmunotherapy treatment for neuroblastoma safe for humans?

The combination of irinotecan, temozolomide, dinutuximab, and GM-CSF has been studied in children with neuroblastoma, showing an acceptable safety profile. Some side effects like diarrhea and myelosuppression (a decrease in bone marrow activity) were observed, but they were manageable. ^{3 4 6 7 8}

What makes the chemoimmunotherapy drug for neuroblastoma unique?

This treatment combines Hu3F8, irinotecan, and temozolomide, which are known to work together effectively against neuroblastoma, with Hu3F8 being an antibody that helps the immune system target cancer cells. The combination is designed to enhance the body's immune response while directly attacking the cancer, offering a novel approach compared to traditional chemotherapy alone. ^{1 3 4 5 8}

Research Team

Shakeel Modak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

References

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

Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma. [2022]

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

Irinotecan plus temozolomide for relapsed or refractory neuroblastoma. [2020]

3. United States 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. [2021]

4. England 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. [2023]

5. United States 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. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Phase I study with irinotecan hydrochloride (CPT-11) for advanced neuroblastoma]. [2018]

7. United States 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. [2022]

8. England 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. [2022]