NK Cell Infusion + Chemotherapy for Neuroblastoma

(STING Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Mark Ranalli

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Nationwide Children's Hospital

Must not be taking: Steroids, CYP3A4 drugs

Disqualifiers: Pregnancy, Other malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new cancer treatment that combines special immune cells with three cancer-fighting drugs. It aims to see if this combination is safe and effective for patients whose cancers are hard to treat with standard therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you must not have taken certain medications like systemic steroids or CYP3A4 inducers/inhibitors for at least 7 days before enrolling.

What data supports the effectiveness of this treatment for neuroblastoma?

Research shows that the combination of irinotecan, temozolomide, dinutuximab, and GM-CSF has demonstrated activity in patients with relapsed or refractory neuroblastoma, with a response rate of 53% in a clinical trial. ^{1 2 3 4 5}

Is the combination of NK Cell Infusion, Chemotherapy, and related treatments safe for humans?

The combination of irinotecan, temozolomide, dinutuximab, and GM-CSF has been studied in children with neuroblastoma, showing an acceptable safety profile with manageable side effects like diarrhea and myelosuppression (a decrease in bone marrow activity). Further research is needed to fully understand the safety of these treatments in combination. ^{1 2 4 5 6}

How is the NK Cell Infusion + Chemotherapy treatment for neuroblastoma different from other treatments?

This treatment is unique because it combines natural killer (NK) cell infusion with chemotherapy drugs irinotecan and temozolomide, which have shown synergy (work better together) against neuroblastoma. The addition of NK cells aims to enhance the immune system's ability to fight cancer, offering a novel approach compared to traditional chemotherapy alone. ^{1 2 3 4 7}

Research Team

Mark Ranalli

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for individuals under 30 years old with neuroblastoma or ganglioneuroblastoma, not just bone marrow disease. They must have adequate organ function and no recent treatments that conflict with the study drugs. Pregnant or breastfeeding individuals, those on certain medications, or with uncontrolled infections cannot participate.

Inclusion Criteria

I have had previous cancer treatment but followed the required waiting periods.

It's been over 2 weeks since my last strong chemotherapy.

My liver is working well.

Exclusion Criteria

I have not been diagnosed with any cancer other than the one I am seeking treatment for.

I do not have any major illnesses that could affect the study treatment or make its side effects worse.

I haven't taken any CYP3A4 affecting drugs in the last week.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 cycles of 21 days each of irinotecan, temozolomide, dinutuximab, sargramostim, and NK cells

18 weeks

Visits every 21 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Dinutuximab (Monoclonal Antibodies)
• Irinotecan (Topoisomerase I inhibitors)
• Natural Killer Cells (CAR T-cell Therapy)
• Sargramostim (Cytokine)
• Temozolomide (Alkylating agents)

Trial Overview The trial tests how safe and tolerable it is to give universal donor NK cells combined with irinotecan, temozolomide, and dinutuximab to patients. It aims to see how well these patients respond after establishing safety in Phase 1 during the expanded Phase 2 cohort.

Participant Groups

Group I: Treatment Experimental Treatment 5 Interventions

The planned therapy will involve 6 cycles of 21 days each consisting of irinotecan, temozolomide, dinutuximab, sargramostim, and natural killer (NK) cells. Treatment cycles will be repeated every 21 days based upon disease response and toxicity criteria. Tumor response will be assessed after Cycles 2, 4 and 6. Patients who do not experience dose-limiting toxicities and achieve complete response, partial response or stable disease may continue to receive the assigned therapy.

Irinotecan is already approved in Japan, Canada for the following indications:

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Catherine Krawczeski

Nationwide Children's Hospital

Chief Medical Officer

MD

Timothy C. Robinson

Nationwide Children's Hospital

Chief Executive Officer since 2019

BSc in Psychology and Business Administration from Indiana University

Findings from Research

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]

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 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]

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]

References

1. 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]

2. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. 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]

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]