Neuroblastoma, Recurrent, RefractoryPhase 1NCT06674265
Safety and Efficacy of Systemic Allogenic NK Cells in R/R Neuroblastoma
A Phase 1 study testing Allogenic NK cells infusion in people with Neuroblastoma, Recurrent, Refractory and Neuroblastoma (NB), run by Marzieh Ebrahimi at 1 site in Iran.
Trial summary
The goal of this clinical trial is to assess safety and efficacy of systemic injection of allogenic NK cells in patients with refractory/recurrent high-risk neuroblastoma. Is the injection of allogenic nk cells safe in patients with R/R high-risk neuroblastoma? Is the injection of allogenic nk cells effective in… Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Neuroblastoma, Recurrent, Refractory, Neuroblastoma (NB), Neuroblastoma in Children
- What is being tested?
- Allogenic NK cells infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIran
- Study dates
- 10 Nov 2024to Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- High-risk neuroblastoma that is resistant to standard induction therapy based on COG (Children's Oncology Group) criteria (according to INRG criteria and having received at least 4 cycles of multi-drug induction chemotherapy, and not responding to conventional treatments).
- Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
- A minimum life expectancy of 6 months.
- Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
- Measurable residual disease based on imaging findings using Curie scoring or MIBG or PET imaging criteria (1: measurable tumor of at least 10 mm in one dimension on MRI or CT scan with positive uptake on I-123 MIBG scan ("MIBG avid") oOR 2): increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET avid")).
- -
Who cannot join
- Insufficient bone marrow function: Platelet count > 50,000/µL, independent of transfusion (no platelet transfusion within one week). Absolute neutrophil count (ANC) maximum of 500 per microliter. Hemoglobin > 10 grams per deciliter.
- Insufficient liver function: Plasma bilirubin level more than 1.5 times the upper limit of normal (ULN). SGPT (ALT) at least three times the upper limit of normal (a level of 45 units per liter is considered the upper limit of normal).
- Insufficient kidney function: Creatinine clearance or estimated radioisotope GFR < 70 ml/min/1.73m². Plasma creatinine level more than 1.5 times the upper limit of normal based on age/gender.
- Insufficient central nervous system function if seizures are present, entry into the study is not possible and if seizures are not well controlled with anticonvulsant drugs.
- 3- Insufficient cardiovascular function Shortening fraction < 27% by ECHO OR Ejection fraction < 50% by ECHO or gated radionuclide study.
- 4- Insufficient pulmonary function evidence of dyspnea at rest. Exercise intolerance. Chronic need for oxygen and room air pulse oximetry < 94% if pulse oximetry evaluation is clinically indicated. Presence of current pleural or pericardial effusion.
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- 5- Inability to tolerate new treatment due to emergency conditions. 6- Elevated catecholamines (more than twice the ULN) or sole involvement of bone marrow (bone marrow positive for NB as the only evaluable disease without confirmatory pathology report).
- 7- Receiving 0.5 mg/kg/day of systemic steroids (equivalent to prednisone) for at least 7 days before enrollment.
- 8- Receiving CYP3A4 inducers or inhibitors at least 7 days before study enrollment.
- 9- Diagnosis of any other malignancy alongside the diagnosis of neuroblastoma. 10- Diarrhea > Grade 2 (4 to 6 stools per day). 11- Significant illness not covered by exclusion criteria but interfering with the study process or increasing the intensity of treatment with NK cells.
- 12- Participation in another clinical trial. 13- Severe impairment of major organ functions, such as renal, cardiac, hepatic, neurological, pulmonary, or gastrointestinal toxicity above Grade 2 according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTC v5.0).
- 14- Inability to comply with protocol requirements. 15- Lack of confirmed and signed consent by the patient's guardians. 16- Evidence of HIV disease (Human Immunodeficiency Virus) or positive serology for HIV.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Iran1 site, 1 recruiting
- Recruiting
Rasoul Akram Hospital
Tehran, 1445613131
Dr. Mohammad Faranoush, Professor, +98 9121590917, faranoush.m@iums.ac.ir
About this study
Official title: Evaluation of Safety and Efficacy Evaluation Post Intravenous Infusion of Activated NK Cells in Recurrent and Refractory High-risk Neuroblastoma Patients
The goal of this clinical trial is to assess safety and efficacy of systemic injection of allogenic NK cells in patients with refractory/recurrent high-risk neuroblastoma.
Is the injection of allogenic nk cells safe in patients with R/R high-risk neuroblastoma? Is the injection of allogenic nk cells effective in patients with R/R high-risk neuroblastoma? We will compare the NK cell administration group with a control group that receives conventional treatment to determine whether the intervention is safe and effective
Read the detailed description
NK cells are isolated from healthy donors through the apheresis process and subsequently separated using the CLINIMACS device in a clean room environment. After quality assessment (sterility, viable cell count, purity, and phenotype of active cells), they are stored at -198°C until use. Upon need, the cells are thawed and washed, followed by checking their viability, count, and sterility. Children between the ages of 2 to 16 who meet the eligibility criteria will be added to the study. After admission, the cells are injected into the patient at a ratio of 5×10^6 cells per kilogram of the patient's body weight. A total of 3 injections are administered to all patients. Based on the patient's response and recovery status, the need for additional injections is evaluated. If improvements in the patient's condition are observed after the last injection and confirmed by MRI MIBG, further 2 injections can continue. The intervals between injections vary based on the patient's standard treatment, and the cells are injected 10 days after the completion of each chemotherapy course.
- Being tested
- Allogenic NK cells infusion
- Keywords
- Neuroblastoma, High-Risk Neuroblastoma, Natural Killer Cell, Nk Cell, adrenal gland
- Medical subject headings
- Neuroblastoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic NK cells infusionBiological
Natural Killer (NK) cells are extracted from a healthy donor through apheresis and processed in a clean room using the CLINIMACS device. After quality assessment, these cells are stored at -198°C until needed. When required, the cells are thawed, washed, and evaluated for viability and sterility before being administered to the patient at a dosage of 5 × 10^6 cells per kilogram of body weight. Two further injections may be considered based on the patient's response and confirmed improvement via MRI MIBG. Injections are scheduled seven to ten days after each chemotherapy course according to the standard treatment protocol.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Group | Active comparator | Patients with refractory/recurrent neuroblastoma will receive 3 to 5 systemic injections of allogeneic NK cells during the intervals between their chemotherapy courses Receives: Biological: Allogenic NK cells infusion |
| Control Group | No intervention | Patients in the control group will receive no cells and just conventional treatments will be administered to them. |
What is being measured
The primary outcome is the main question the study is designed to answer.
NK Cell Infusion Safety
The safety of the treatment is assessed using the Common Terminology Criteria for Adverse Events (CTCAE) checklist.
Measured: After each injection to next injection and 2 weeks after last injection
Secondary outcomes (1)
Response rate comparison between control and intervention groups
The response rate in patients in the control and treatment groups will be assessed and compared using MRI, MIBG, or PET scans.
Measured: 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2024
- Study start10 Nov 2024
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroblastoma, Recurrent, RefractoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marzieh Ebrahimi
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Royan Institute, Iran University of Medical Sciences
- Responsible party
- Sponsor-investigator, Marzieh Ebrahimi, Kian Immune Cell Company
- Investigators
- Dr. Marzieh Ebrahimi, PhD. in Medical Immunology, Study chair, Royan InstituteDr. Mohammad Faranoush, Pediatric Oncologist, Principal investigator, Iran University of Medical Science
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06674265
- Sponsor's protocol ID
- IR.ACECR.ROYAN.REC.1400.032
- Status last verified
- Apr 2025
- First submitted
- 3 Nov 2024
- Last updated
- 9 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety and Efficacy Evaluation Post Intravenous Infusion of Activated NK Cells in Recurrent and Refractory High-risk Neuroblastoma Patients
- ClinicalTrials.gov ID
- NCT06674265
- Acronym / sponsor ID
- IR.ACECR.ROYAN.REC.1400.032
- Keywords
- Neuroblastoma, High-Risk Neuroblastoma, Natural Killer Cell, Nk Cell, adrenal gland
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Marzieh EbrahimiIndustry (pharma, biotech, devices)
- Collaborators
- Royan Institute, Iran University of Medical Sciences
- Study start
- 10 Nov 2024 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 5 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to assess safety and efficacy of systemic injection of allogenic NK cells in patients with refractory/recurrent high-risk neuroblastoma.
Is the injection of allogenic nk cells safe in patients with R/R high-risk neuroblastoma? Is the injection of allogenic nk cells effective in patients with R/R high-risk neuroblastoma? We will compare the NK cell administration group with a control group that receives conventional treatment to determine whether the intervention is safe and effective
Detailed description
NK cells are isolated from healthy donors through the apheresis process and subsequently separated using the CLINIMACS device in a clean room environment. After quality assessment (sterility, viable cell count, purity, and phenotype of active cells), they are stored at -198°C until use. Upon need, the cells are thawed and washed, followed by checking their viability, count, and sterility. Children between the ages of 2 to 16 who meet the eligibility criteria will be added to the study. After admission, the cells are injected into the patient at a ratio of 5×10^6 cells per kilogram of the patient's body weight. A total of 3 injections are administered to all patients. Based on the patient's response and recovery status, the need for additional injections is evaluated. If improvements in the patient's condition are observed after the last injection and confirmed by MRI MIBG, further 2 injections can continue. The intervals between injections vary based on the patient's standard treatment, and the cells are injected 10 days after the completion of each chemotherapy course.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Group | Active comparator | Biological: Allogenic NK cells infusionPatients with refractory/recurrent neuroblastoma will receive 3 to 5 systemic injections of allogeneic NK cells during the intervals between their chemotherapy courses |
| Control Group | No intervention | –Patients in the control group will receive no cells and just conventional treatments will be administered to them. |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- High-risk neuroblastoma that is resistant to standard induction therapy based on COG (Children's Oncology Group) criteria (according to INRG criteria and having received at least 4 cycles of multi-drug induction chemotherapy, and not responding to conventional treatments).
- Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem cell transplantation or aggressive therapy.
- A minimum life expectancy of 6 months.
- Patients must have a pathological diagnosis of neuroblastoma and/or confirmation of tumor cells in the bone marrow with increased urinary catecholamines.
- Measurable residual disease based on imaging findings using Curie scoring or MIBG or PET imaging criteria (1: measurable tumor of at least 10 mm in one dimension on MRI or CT scan with positive uptake on I-123 MIBG scan ("MIBG avid") oOR 2): increased FDG uptake on 18F-FDG PET-CT or PET-MRI ("PET avid")).
Key exclusion criteria (12 listed)
- Insufficient bone marrow function: Platelet count > 50,000/µL, independent of transfusion (no platelet transfusion within one week). Absolute neutrophil count (ANC) maximum of 500 per microliter. Hemoglobin > 10 grams per deciliter.
- Insufficient liver function: Plasma bilirubin level more than 1.5 times the upper limit of normal (ULN). SGPT (ALT) at least three times the upper limit of normal (a level of 45 units per liter is considered the upper limit of normal).
- Insufficient kidney function: Creatinine clearance or estimated radioisotope GFR < 70 ml/min/1.73m². Plasma creatinine level more than 1.5 times the upper limit of normal based on age/gender.
- Insufficient central nervous system function if seizures are present, entry into the study is not possible and if seizures are not well controlled with anticonvulsant drugs.
- 3- Insufficient cardiovascular function Shortening fraction < 27% by ECHO OR Ejection fraction < 50% by ECHO or gated radionuclide study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogenic NK cells infusionNatural Killer (NK) cells are extracted from a healthy donor through apheresis and processed in a clean room using the CLINIMACS device. After quality assessment, these cells are stored at -198°C until needed. When required, the cells are thawed, washed, and evaluated for viability and sterility before being administered to the patient at a dosage of 5 × 10^6 cells per kilogram of body weight. Two further injections may be considered based on the patient's response and confirmed improvement via MRI MIBG. Injections are scheduled seven to ten days after each chemotherapy course according to the standard treatment protocol. | Biological | Intervention Group |
Primary outcome
NK Cell Infusion Safety
Time frame: After each injection to next injection and 2 weeks after last injection
The safety of the treatment is assessed using the Common Terminology Criteria for Adverse Events (CTCAE) checklist.
1 secondary outcome
Response rate comparison between control and intervention groups
Time frame: 6 months and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr. Marzieh Ebrahimi, PhD. in Medical Immunology study chair
Royan Institute
Dr. Mohammad Faranoush, Pediatric Oncologist principal investigator
Iran University of Medical Science
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogenic NK cells infusion in people with Neuroblastoma, Recurrent, Refractory and Neuroblastoma (NB), run by Marzieh Ebrahimi at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dr. Marzieh Ebrahimi (+98 9123448359, m.ebrahimi@royan-rc.ac.ir), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NK Cell Infusion Safety (time frame: After each injection to next injection and 2 weeks after last injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.