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}

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 United States, European Union, Japan, Canada for the following indications:

🇺🇸 Approved in United States as Camptosar for:

• Colorectal cancer

🇪🇺 Approved in European Union as Irinotecan for:

• Colorectal cancer

🇯🇵 Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

🇨🇦 Approved in Canada as Irinotecan for:

• Colorectal cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Nationwide Children's Hospital Columbus, OH

Who Is Running the Clinical Trial?

Nationwide Children's Hospital Lead Sponsor

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] The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF.

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] In the Children's Oncology Group ANBL1221 phase 2 trial for patients with first relapse/first declaration of refractory high-risk neuroblastoma, irinotecan and temozolomide (I/T) combined with either temsirolimus (TEMS) or immunotherapy (the anti-GD2 antibody dinutuximab (DIN) and granulocyte macrophage colony stimulating factory (GM-CSF)) was administered. The response rate among patients treated with I/T/DIN/GM-CSF in the initial cohort (n=17) was 53%; additional patients were enrolled to permit further evaluation of this chemoimmunotherapy regimen. Potential associations between immune-related biomarkers and clinical outcomes including response and survival were evaluated.

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

Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma. [2022] The combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed and refractory neuroblastoma (NB).

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] Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma.

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] Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma.

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

[Phase I study with irinotecan hydrochloride (CPT-11) for advanced neuroblastoma]. [2018] A Phase I trial of irinotecan hydrochloride (CPT-11) was performed to determine the maximum tolerated dose (MTD), the dose-limiting toxicities, and the incidence and severity of other toxicities in children with advanced neuroblastoma. Three children received 11 courses of CPT-11 administered as a 90-min i.v. infusion, daily for 3 days every 21 days. Doses ranged from 100 mg/m2 to 220 mg/m2. Two peaks in the total number of instances of diarrhea was observed, 25 stools at 3 days and 32 stools at 10 days. Myelosuppression was well controlled and of brief duration. One child achieved a clinical complete response (CR) and 2 had a partial response (PR). The MTD of CPT-11 administration was 180 mg/m2 for 3 days. These results indicate the usefulness of CPT-11 for the treatment of advanced neuroblastoma. Further investigation is necessary to establish its role in combination chemotherapeutic regimens.

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] This phase II study was conducted to determine the response rate associated with use of irinotecan and temozolomide for children with relapsed/refractory neuroblastoma.