A Phase 3 interventional study of Dinutuximab beta, temozolomide, irinotecan, autologous NK cell and irinotecan, temozolomide, dinutuximab beta, NK-cell product in Neuroblastoma (NB) and Ganglioneuroblastoma, sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology. Recruiting at 1 site in Russia. Open to participants aged 18 Months to 18 Years. Per ClinicalTrials.gov, last updated 2026-01-29.
Sponsored by Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Phase 3, Interventional, and Treatment
Neuroblastoma (NB) is a malignant neoplasm of the sympathetic nervous system, occurring in 1 in 8,000 live births, accounting for 6-10% of all childhood malignant neoplasms and responsible for 12-15% of mortality -, making it the most common and life-threatening extracranial tumor in childhood.
Patients with stage 4 high-risk NB is the subgroup with the poorest prognosis. Within this group, two subgroups with an extremely unfavorable disease course are distinguished: patients with a poor response to the induction phase of therapy (refractory disease) and patients with relapsed or progressive disease.
Nowadays, 10-15% of patients show a poor end-induction response, whereas achieving a good end-induction response associated with better long-term survival. Improvement of the response to induction therapy may contribute to better treatment outcomes in newly diagnosed high-risk NB patients and can be achieved by intensification of the induction phase to decrease the number of patients with refractory disease. Also intensification of the second-line therapy may contribute to better responses in patients with relapsed and progressive disease.
Protocol aimed to overcome heterogeneous tumor drug resistance through the synergistic interaction of cytostatic and immunobiological agents in combination with NK cell therapy.
This approach combines cytotoxic agents with anti-GD2 monoclonal antibodies (mAb) to enhance antitumor activity. Cultured, ex vivo-activated autologous NK cells are infused to compensate for effector cell depletion during therapy and to augment antibody-dependent cellular cytotoxicity (ADCC), potentially improving clinical outcomes.
This comprehensive approach opens novel prospects for enhancing treatment efficacy in patients with refractory and relapsed high-risk NB.
The expected outcomes of this protocol include a significant increase in therapeutic efficacy indicators - objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and relapse-free survival (RFS), as well as in patient quality of life.
The study design evaluates a therapeutic interventionin two independent groups:
Intervention plan for patients with a refractory NB (arm A):
Patients who meet the inclusion criteria will undergo an intensified induction phase within the framework of this clinical trial protocol, while the preceding induction phase and subsequent consolidation and post-consolidation phases will be performed outside of this protocol in accordance with the current clinical practice. As part of the intensified induction, a procedure for the collection of mononuclear cells for the cultivation and expansion of the autologous NK cell product (Day -1) is planned, followed by one course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and four courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + NK-cell product), with an inter-cycle interval of 21 days. Transfusion of the autologous NK cell product will be performed on Day 7 of each DIT course.
Intervention plan for patients with relapsed/progression (arm В):
Patients who meet the inclusion criteria will undergo peripheral blood collection with subsequent isolation of mononuclear cells for cultivation and expansion of an autologous NK cell product (Day -1), followed by administration of the first course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and five courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + autologous NK cell product) with a 21-day inter-cycle interval within the framework of this clinical trial protocol. Subsequent phases of therapy (including delayed surgery and external beam radiotherapy) will be carried out after completion of the chemoimmunotherapy in combination with autologous NK cell therapy, outside the present protocol, in accordance with current clinical practice. Transfusion of the autologous NK cell product will be performed on Day 7 of each DIT course.
21 studies on the registry are indexed under Ganglioneuroblastoma; 10 are open to participants now.
This study's planned enrollment of 5 is below the median of 69 across 16 interventional studies indexed under Ganglioneuroblastoma.
Browse Ganglioneuroblastoma studies →Federal Research Institute of Pediatric Hematology, Oncology and Immunology is the lead sponsor of 57 studies on the registry; 18 are open to participants now.
Compared within Ganglioneuroblastoma, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Neuroblastoma. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients stratified to the high-risk group according to the criteria of the German Society of Pediatric Oncology and Hematology (GPOH) - NB 2004, aged from 18 months to 18 years, and meeting the following conditions:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients who meet the inclusion criteria will undergo an intensified induction phase within the framework of this clinical trial protocol, while the preceding induction phase and subsequent consolidation and post-consolidation phases will be performed outside of this protocol in accordance with the current clinical practice. As part of the intensified induction, a procedure for the collection of mononuclear cells for the cultivation and expansion of the autologous NK cell product (Day -1) is planned, followed by one course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and four courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + NK-cell product)
Combination Product: Dinutuximab beta, temozolomide, irinotecan, autologous NK cell · Combination Product: irinotecan, temozolomide, dinutuximab beta, NK-cell product
Patients who meet the inclusion criteria will undergo peripheral blood collection with subsequent isolation of mononuclear cells for cultivation and expansion of an autologous NK cell product (Day -1), followed by administration of the first course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and five courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + autologous NK cell product)
Combination Product: Dinutuximab beta, temozolomide, irinotecan, autologous NK cell · Combination Product: irinotecan, temozolomide, dinutuximab beta, NK-cell product
As part of the intensified induction, a procedure for the collection of mononuclear cells for the cultivation and expansion of the autologous NK cell product (Day -1) is planned, followed by one course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and four courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + NK-cell product), with an inter-cycle interval of 21 days. Transfusion of the autologous NK cell product will be performed on Day 7 of each DIT course.
Drug pages: Irinotecan · Temozolomide · Dinutuximab · Natural Killer Cell
Patients who meet the inclusion criteria will undergo an intensified induction phase within the framework of this clinical trial protocol, while the preceding induction phase and subsequent consolidation and post-consolidation phases will be performed outside of this protocol in accordance with the current clinical practice. As part of the intensified induction, a procedure for the collection of mononuclear cells for the cultivation and expansion of the autologous NK cell product (Day -1) is planned, followed by one course of chemotherapy according to the IT regimen (irinotecan + temozolomide) and four courses of chemoimmunotherapy in combination with autologous NK cell therapy according to the DIT regimen (irinotecan + temozolomide + dinutuximab beta + NK-cell product)
Tolerability and toxicity of chemoimmunotherapy in combination with NK cell therapy.
(Proportion of patients receiving at least 80% of the planned doses without grade ≥ 3 adverse immunological reactions (ADRs) related to the NK cell product, assessed acc
Time frame: immediately after completion of courses of chemoimmunotherapy in combination with NK cell therapy.
ORR after completion of chemoimmunotherapy courses in combination with NK cell therapy.
(The proportion of patients with a good response (CR, VGPR and PR) to therapy, assessed in accordance with the International Response Criteria for Patients with NB)
Time frame: immediately after completion of courses of chemoimmunotherapy in combination with
ORR after completion of study therapy.
(The proportion of patients who achieved a good response (CR, VGPR and PR) to therapy, assessed in accordance with the International Response Criteria for Patients with NB)).
Time frame: immediately after completion of study therapy.
OS and EFS at 1 year, 3 years, and 5 years after completion of study therapy.
For patients with refractory disease: The proportion of surviving patients, regardless of disease status (for OS) and the proportion of patients without adverse events, such as relapse, progression or death (for EFS)).
Time frame: 1 year, 3 years, and 5 years from the date of diagnosis.
OS, PFS, and RFS at 1 and 3 years after completion of the study therapy.
For patients with progression/relapsed disease: The proportion of surviving patients from the time of diagnosis, regardless of disease status (for OS); the proportion of patients without disease relapse (for RFS) or disease progression (for PFS) from the time of the relapse or progression).
Time frame: are 1, 3, and 5 years from the date of diagnosis (for OS) or from the date of documented progression/relapse (for PFS and RFS)).
Plan to share: No
No publications or documents are linked to this record.
Started Nov 2025 (actual). Primary completion is estimated for Dec 2026, 12 months after the start.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Irinotecan · Temozolomide · Dinutuximab · Natural Killer Cell
Federal Research Institute of Pediatric Hematology, Oncology and Immunology