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.
Is the drug combination of Irinotecan, Natural Killer Cells, and Temozolomide promising for treating neuroblastoma?Yes, the combination of these drugs has shown promise in treating neuroblastoma, especially in cases where the disease has returned or is resistant to other treatments. Studies have reported positive response rates, indicating that this drug combination could be effective for patients with challenging forms of neuroblastoma.23567
What safety data exists for NK Cell Infusion + Chemotherapy for Neuroblastoma?The combination of irinotecan, temozolomide, dinutuximab, and GM-CSF has been studied in the Children's Oncology Group ANBL1221 trial for relapsed/refractory neuroblastoma. The trial reported a 53% response rate in the initial cohort and further evaluated the regimen's toxicity. Irinotecan and temozolomide have shown acceptable toxicity profiles, making them suitable for combination with new agents like dinutuximab. A Phase I trial of irinotecan (CPT-11) identified diarrhea and myelosuppression as dose-limiting toxicities, with a maximum tolerated dose of 180 mg/m2 for 3 days. These studies indicate the regimen's potential efficacy and manageable safety profile, but further investigation is needed.12457
What data supports the idea that NK Cell Infusion + Chemotherapy for Neuroblastoma is an effective treatment?The available research shows that the combination of irinotecan, temozolomide, dinutuximab, and GM-CSF (a type of immune system booster) has shown positive results in treating children with relapsed or hard-to-treat neuroblastoma. In one study, 53% of patients responded to this treatment, which is a significant outcome for this challenging condition. This suggests that NK Cell Infusion + Chemotherapy can be an effective option for patients who have not responded to other treatments.24567
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop all current medications. However, you must not have taken systemic steroids or CYP3A4 inducers/inhibitors for at least 7 days before enrollment. Also, you should not have received irinotecan or temozolomide in the last 6 months.
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
It's been over 2 weeks since my last strong chemotherapy.
My cancer has returned or worsened despite treatment.
My liver is functioning well, with normal bilirubin and ALT levels.
I am under 30 years old.
My heart's pumping ability is confirmed to be good by a heart scan.
My cancer is confirmed as neuroblastoma or ganglioneuroblastoma with specific urine markers.
My tumor can be seen on scans and shows activity on specific tests.
My cancer got worse during my first intense treatment.
My blood tests show enough neutrophils and platelets, and I haven't used specific growth factors recently.
I don't need oxygen regularly and can breathe well at rest.
My kidney function is within the required range.
It's been over 4 weeks since I completed radiation on a targeted lesion.
It has been over 6 weeks since my last MIBG therapy.
My kidney function, measured by creatinine, is within the normal range for my age and gender.
I haven't taken irinotecan or temozolomide in the last 6 months.
I don't have trouble breathing at rest, don't need extra oxygen, and my oxygen levels are good.
My condition has come back after treatment.
I have had a stem cell infusion treated with a special process.
My liver enzyme (ALT) levels are within the required range for the study.
My diagnosis is neuroblastoma or ganglioneuroblastoma, confirmed by tests.
It has been over 6 weeks since my last cellular therapy treatment.
My brain-related side effects are mild.
My cancer did not fully respond after 4 rounds of initial chemotherapy.
I have received anti-GD2 monoclonal antibodies before.
I am under 30 years old.
My bilirubin levels are within normal range for my age.
I have had a stem cell infusion treated with a special process.
Exclusion Criteria
I have not been diagnosed with any cancer other than the one I am seeking treatment for.
I do not have any infections that aren't responding to treatment.
I do not have severe diarrhea.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: TreatmentExperimental Treatment5 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 nearbySelect from list below to view details:
Nationwide Children's HospitalColumbus, OH
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Who is running the clinical trial?
Nationwide Children's HospitalLead Sponsor
References
[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.
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.
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.
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.
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.
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).
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.