NK Cell Infusions for Relapsed/Refractory Neuroblastoma
This study is testing a new combination treatment for children and young adults (up to age 29) with relapsed or refractory (hard-to-treat) neuroblastoma. It combines special immune cells called Natural Killer (NK) cells with chemotherapy drugs Irinotecan and Temozolomide, and another drug called Dinutuximab. The study aims to see how safe this combination is and how well it works to shrink tumors. You may be eligible if you have neuroblastoma that has come back or is not responding to other treatments, and have a life expectancy of more than two months. The study will look at side effects and how your tumors respond to treatment using scans like CT, MRI, and MIBG.
- Study design
- This is a Phase 1 study with a Phase 2 expansion, meaning it first checks for safety and then how well the treatment works. It plans to enroll 31 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track side effects for 12 months and tumor response for 24 months after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04211675
NK Cells Infusions With Irinotecan, Temozolomide, and Dinutuximab
Recruiting
PHASE1Up to 29InterventionalTreatmentNationwide Children's HospitalInvestigator-initiated
~31 participants
Updated 2025-05-13 on ClinicalTrials.gov
What's tested:Natural Killer CellsTemozolomideIrinotecanDinutuximabSargramostim
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
NK cells safety and tolerability: Number of participants with treatment-related adverse events and toxicities
Measured over 12 months
+3 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesOhio1
Study leadership
- Mark Ranalli, MD · PRINCIPAL_INVESTIGATOR · Nationwide Children's Hospital
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Less than 30 years of age when registered on the study.
Patients must have a histologic verification of neuroblastoma (NBL) or ganglioneuroblastoma or NBL cells in bone marrow with or without elevated urine catecholamines.
Life expectancy \>2 months, AND one of the following:
Recurrent disease; or
First episode of progressive disease (new lesion, increase in size, previous negative bone marrow) during initial multi-drug, induction myelosuppressive therapy; or
Primary resistant/refractory disease (partial, mixed, stable response criteria met) after completing at least 4 cycles of induction multi-drug induction chemotherapy
One of the following:
Patients must have measurable or evaluable tumor defined as: a) Measurable tumor on MRI or CT obtained within 4 weeks prior to study entry; Measurable is defined as ≥ 10mm in at least one dimension AND that has positive uptake on I-123 MIBG scan ("MIBG avid") or demonstrates increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET-avid"); OR b) Evaluable tumor by I-123 MIBG scan within 4 weeks prior to study entry, defined as positive uptake at a minimum of one site;
Measurable or evaluable disease must represent recurrent disease after therapy completion or progressive disease on therapy or refractory disease during induction;
Patients with refractory disease that are not avid on MIBG scan and do not have increased FDG uptake on PET must have biopsy proven viable NBL;
New soft tissue sites that are MIBG avid or PET avid do not require biopsy as long as initial histologically-confirmed NBL diagnosis prior to current therapy
Patients must have progressed during or following completion of frontline therapy. Agents considered to be a part of frontline therapy would include chemotherapy, radiation therapy, autologous stem cell transplantation, retinoids, immunotherapy with anti GD2 agents, cellular therapies, or I-131 MIBG, and frontline therapy is defined as any combination of these agents defined in published regimens or current cooperative group clinical trials for the successful treatment of that cancer. Therapy may not have been received more recently than the timeframes defined below:
Myelosuppressive chemotherapy: At least 14 days since completion of myelosuppressive therapy
Biologic: At least 7 days since completion of therapy with non-myelosuppressive biologic or retinoid
Radiation: At least 4 weeks since completion of radiation to any site identified as a target lesion. Palliative radiation is allowed to sites not used to measure response
Stem Cell Transplant (SCT): At least 6 weeks after autologous stem cell transplant or stem cell infusions as long as hematologic criteria have been met
131I-MIBG Therapy: At least 6 weeks after therapeutic MIBG treatment
Cellular therapies: At least 6 weeks after any cellular therapy treatment (e.g., prior NK, CAR-T therapy)
Adequate bone marrow function, defined as:
Peripheral absolute neutrophil count (ANC) ≥500/microL. Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days or short-acting myeloid growth factors (e.g., Neupogen) within 7 days of study entry.
Platelet count ≥50,000/microL (transfusion independent for at least 1 week)
Adequate renal function defined as:
Creatinine clearance or estimated radioisotope GFR ≥70 ml/min/1.73m2 or
Serum creatinine \< 2x upper limit of normal (ULN) based on age/gender
Adequate liver function defined as:
Total bilirubin \<1.5x ULN for age AND
SGPT (ALT) ≤5x ULN for age (or ≤225 U/L). For purpose of this study, the ULN for SGPT (ALT) is 45 U/L.
Adequate central nervous system function defined as:
Patients with seizure disorders may be enrolled if seizures are well controlled on anti-convulsants
CNS toxicity ≤ Grade 2
Adequate cardiac function defined as:
Shortening fraction of ≥ 27% by ECHO OR
Ejection fraction ≥ 50% by ECHO or gated radionuclide study
Adequate pulmonary function defined as:
No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry \> 94% if there is a clinical indication for pulse oximetry
Exclusion
Patients who are pregnant or breastfeeding
Patients with elevated catecholamines (\>2x ULN) only.
Patients must not have received 0.5 mg/ kg/ day (prednisone equivalent) doses of systemic steroids for at least 7 days prior to enrollment.
Patients must not have received CYP3A4 inducer or inhibitor for at least 7 days prior to study enrollment.
Patients must not have been diagnosed with any other malignancy.
Patients must not have \> Grade 2 diarrhea.
Patients must not have uncontrolled infection.
Patients with history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of anti-GD2 therapy.
What this trial measures
- NK cells safety and tolerability: Number of participants with treatment-related adverse events and toxicities12 months
Number of participants with treatment-related adverse events and toxicities as assessed by CTCAE v4.0
- Response to NK Cell treatment as determine by CT/MRI imaging24 months
To estimate the response to treatment, as determined by disease status evaluated using CT/MRI scans through the measuring tool RECIST.
- Response to NK Cell treatment as determine by MIBG scans imaging24 months
To estimate the response to treatment, as determined by disease status evaluated using MIBG scans through the Curie score system.
- Response to NK Cell treatment as determine by bone marrow aspiration24 months
To estimate the response to treatment, as determined by disease status evaluated using bone marrow aspiration and biopsy through H\&E stain. RECIST.