A Phase 3 interventional study of Biospecimen Collection and Bone Marrow Aspiration in Ganglioneuroblastoma, Nodular and Neuroblastoma, sponsored by National Cancer Institute (NCI). Recruiting at 180 sites in 5 countries. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2026-10-30.
Sponsored by National Cancer Institute (NCI) · Phase 3, Interventional, and Treatment
This phase III trial tests how well the addition of dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy works for treating children with newly diagnosed high-risk neuroblastoma. Dinutuximab is a monoclonal antibody that binds to a molecule called GD2, which is found on the surface of neuroblastoma cells, but is not present on many healthy or normal cells in the body. When dinutuximab binds to the neuroblastoma cells, it helps signal the immune system to kill the tumor cells. This helps the cells of the immune system kill the cancer cells, this is a type of immunotherapy. When chemotherapy and immunotherapy are given together, during the same treatment cycle, it is called chemoimmunotherapy. This clinical trial randomly assigns patients to receive either standard chemotherapy and surgery or chemoimmunotherapy (chemotherapy plus dinutuximab) and surgery during Induction therapy. Chemotherapy drugs administered during Induction include, cyclophosphamide, topotecan, cisplatin, etoposide, vincristine, and doxorubicin. These drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing or by stopping them from spreading. Upon completion of 5 cycles of Induction therapy, a disease evaluation is completed to determine how well the treatment worked. If the tumor responds to therapy, patients receive a tandem transplantation with stem cell rescue. If the tumor has little improvement or worsens, patients receive chemoimmunotherapy on Extended Induction. During Extended Induction, dinutuximab is given with irinotecan, temozolomide. Patients with a good response to therapy move on to Consolidation therapy, when very high doses of chemotherapy are given at two separate points to kill any remaining cancer cells. Following, transplant, radiation therapy is given to the site where the cancer originated (primary site) and to any other areas that are still active at the end of Induction. The final stage of therapy is Post-Consolidation. During Post-Consolidation, dinutuximab is given with isotretinoin, with the goal of maintaining the response achieved with the previous therapy. Adding dinutuximab to Induction chemotherapy along with standard of care surgical resection of the primary tumor, radiation, stem cell transplantation, and immunotherapy may be better at treating children with newly diagnosed high-risk neuroblastoma.
PRIMARY OBJECTIVE:
I. To determine if the event-free survival (EFS) of patients with newly diagnosed high-risk neuroblastoma assigned to early chemoimmunotherapy during Induction differs from that of patients who are not assigned to treatment that includes early chemoimmunotherapy.
SECONDARY OBJECTIVES:
I. To determine if early chemoimmunotherapy during Induction therapy improves end of Induction (EOI) response rates and overall survival (OS) for patients with newly diagnosed high-risk neuroblastoma.
II. To determine response rates, EFS, and OS following an Extended Induction regimen with chemoimmunotherapy in patients with progressive disease or a poor response to Induction therapy.
III. To compare the toxicities experienced by patients treated with chemoimmunotherapy during Induction versus those experienced by patients treated with standard Induction and to describe toxicities experienced during Extended Induction.
IV. To determine GD2 expression on tumor tissue and tumor cells in bone marrow and assess for associations with response and outcome.
EXPLORATORY OBJECTIVES:
I. To describe the association between tumor and host factors and outcomes in patients receiving protocol therapy.
II. To evaluate circulating biomarkers and markers of minimal residual disease at baseline and during therapy, and assess for associations with response and outcome.
III. To compare patterns of failure between patients treated with and without dinutuximab during induction.
IV. To determine the effect of telomere maintenance mechanisms on end of Induction response rates, EFS, and OS.
V. To explore the impact of high-risk neuroblastoma (HRNBL) and its therapy, including the addition of dinutuximab to Induction chemotherapy, on functional and quality of life outcomes in patients with HRNBL, as measured by caregiver (parent/legal guardian) and patient questionnaires.
VI. To describe the adequacy of diagnostic biopsy specimens, including those obtained by percutaneous core needle biopsy.
VII. To explore the associations between family-reported adverse social determinants of health and both clinical outcomes and biology.
VIII. To develop and validate deep learning predictors of Induction response based on diagnostic MIBG scans. (Imaging Objective) IX. To compare institutional versus central determination of overall response, individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease), and poor end of induction response (PEIR) and good end of induction response (GEIR) determination. (Imaging Objective) X. To describe late toxicities (including impaired organ function, neuropsychiatric toxicity, and incidence of secondary malignancy) in patients treated with dinutuximab during Induction or Extended Induction to late toxicities in patients who have not received dinutuximab during these phases of therapy.
XI. To evaluate whether reduced dose radiotherapy to the primary site clinical target volume (CTV) in patients with complete response of the primary site at EOI results in comparable local control relative to historical cohorts.
XII. To compare post-transplant complications between treatment arms, and assess for associations with outcome.
XIII. To assess for associations between EOI response (including good end of Induction response [GEIR] and poor end of Induction response [PEIR]) and individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease) with outcome (EFS and OS).
XIV. To describe and compare the changes in image-defined risk factors (IDRFs) between patients treated with and without dinutuximab during Induction and associate with surgical outcomes and local failure rates following primary tumor resection.
XV. To bank serial samples of blood, bone marrow, and tumor tissue for future research.
OUTLINE: Patients receive Induction cycle 1 and are then randomized to 1 of 2 treatment arms.
INDUCTION CYCLE 1: Patients receive cyclophosphamide intravenously (IV) over 30 minutes and topotecan IV over 30 minutes on days 1-5 in the absence of unacceptable toxicity.
ARM A:
INDUCTION CYCLES 2-5: Patients receive cyclophosphamide IV over 30 minutes and topotecan IV over 30 minutes on days 1-5 of cycle 2 in the absence of unacceptable toxicity. Patients then undergo stem cell harvest via apheresis. Patients then receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 of cycles 3 and 5, and vincristine IV on day 1, doxorubicin IV over 15 minutes, and cyclophosphamide IV over 1 hour on days 1-2 of cycle 4 in the absence of unacceptable toxicity. Patients undergo primary tumor resection after Induction cycle 4 or 5. Following Induction cycle 5, patients undergo testing to determine response to Induction therapy. Patients with a good tumor response proceed to Consolidation, while patients with a poor tumor response proceed to Extended Induction.
EXTENDED INDUCTION: Patients with a poor tumor response or progression during Induction receive temozolomide orally (PO), via nasogastric tube (NG), or via gastric tube (G-tube) on days 1-5, irinotecan IV over 90 minutes on days 1-5, and dinutuximab IV over 10 hours. Treatment repeats every 21 days for up to a maximum of 6 cycles in the absence of disease progression or unacceptable toxicity. If at any time during Extended Induction testing shows a good tumor response, patients proceed to Consolidation. If after 6 cycles of Extended Induction or if at any time progression is noted, patients are removed from the study.
CONSOLIDATION: Patients undergo two autologous hematopoietic stem cell transplantations (HSCTs) during Consolidation. Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2 during HSCT 1. Patients then receive stem cell infusion IV on day 0. Between 6 and 10 weeks after stem cell infusion, patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin over 24 hours on days -7 to -4 during HSCT 2. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after HSCT 2. Patients receive radiation daily for 12 treatments in the absence of disease progression or unacceptable toxicity.
POST CONSOLIDATION: Patients receive dinutuximab IV over 10 hours on days 4-7 and isotretinoin PO twice daily (BID) on days 11-24 of cycles 1-5. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive isotretinoin PO BID on days 15-28 for 1 additional cycle, cycle 6.
Patients undergo blood and urine sample collection, echocardiogram (ECHO) or multigated acquisition scan (MUGA), bone marrow aspiration and/or biopsy, computed tomography (CT) scan, magnetic resonance imaging (MRI), iodine-123 meta-iodobenzylguanidine (I-MIBG) scan and possible fluorodeoxyglucose position emission tomography (FDG-PET) scan throughout the study.
ARM B:
INDUCTION CYCLES 2-5: Patients receive cyclophosphamide IV over 30 minutes, topotecan IV over 30 minutes on days 1-5, and dinutuximab IV over 10 hours on days 2-5 of cycle 2 in the absence of unacceptable toxicity. Patients then undergo stem cell harvest via apheresis. Patients receive cisplatin IV over 4 hours and etoposide IV over 2 hours on days 1-3 and dinutuximab IV over 10 hours on days 2-5 of cycles 3 and 5, and vincristine IV on day 1, doxorubicin IV over 15 minutes, and cyclophosphamide IV over 1 hour on days 1-2, and dinutuximab IV over 10 hours on days 2-5 of cycle 4 in the absence of unacceptable toxicity. Patients undergo primary tumor resection after Induction cycle 4 or 5. Following Induction cycle 5, patients undergo testing to determine response to Induction therapy. Patients with a good tumor response proceed to Consolidation, while patients with a poor tumor response proceed to Extended Induction.
EXTENDED INDUCTION: Patients with a poor tumor response or progression during Induction receive temozolomide PO, via NG tube, or via G-tube on days 1-5, irinotecan IV over 90 minutes on days 1-5, and dinutuximab IV over 10 hours. Treatment repeats every 21 days for up to a maximum of 6 cycles in the absence of disease progression or unacceptable toxicity. If at any time during Extended Induction testing shows a good tumor response, patients proceed to Consolidation. If after 6 cycles of Extended Induction or if at any time progression is noted, patients are removed from the study.
CONSOLIDATION: Patients undergo two autologous HSCTs during Consolidation. Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2 during HSCT 1. Patients then receive stem cell infusion IV on day 0. Between 6 and 10 weeks after stem cell infusion patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin over 24 hours on days -7 to -4 during HSCT 2. Patients receive stem cell infusion IV on day 0. Between day +42 and day +80 after HSCT 2, patients receive radiation daily for 12 treatments in the absence of disease progression or unacceptable toxicity.
POST CONSOLIDATION: Patients receive dinutuximab IV over 10 hours on days 4-7 and isotretinoin PO BID on days 11-24 of cycles 1-5. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive isotretinoin PO BID on days 15-28 for 1 additional cycle, cycle 6.
Patients undergo blood and urine sample collection, ECHO or MUGA, bone marrow aspiration and/or biopsy, CT scan, MRI, I-MIBG scan and possible FDG-PET scan throughout the study.
After completion of study treatment, patients are followed up at 3, 6, 9,12, 15, 18, 24, 30, 36, 42, 48, 54, and 60 months and then periodically for up to 10 years from enrollment.
21 studies on the registry are indexed under Ganglioneuroblastoma; 10 are open to participants now.
This study's planned enrollment of 478 is above the median of 69 across 16 interventional studies indexed under Ganglioneuroblastoma.
Browse Ganglioneuroblastoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
* Must have a diagnosis of neuroblastoma (NBL) or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamines
Newly diagnosed, high risk neuroblastoma (HRNBL) defined as one of the following:
No prior anti-cancer therapy except as outlined below:
A serum creatinine based on age/sex as follows:
≥ 16 years: Male 1.7 mg/dL and female 1.4 mg/dL
or a GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method or direct small molecule clearance method (iothalamate or other molecule per institutional standard)
Serum glutamic pyruvic transaminase () (Alanine aminotransferase [ALT]) ≤ 10 x ULN*
* Shortening fraction of ≥ 27% by echocardiogram, or
No known to PBSC collection. Examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
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.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
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.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
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.
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 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.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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.
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.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
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.
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.
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.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask 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.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
See detailed description
Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Carboplatin · Drug: Cisplatin · Procedure: Computed Tomography · Drug: Cyclophosphamide · Biological: Dinutuximab · Drug: Doxorubicin · Procedure: Echocardiography Test · Drug: Etoposide · Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan · Procedure: Hematopoietic Cell Transplantation · Drug: Irinotecan · Drug: Isotretinoin · Procedure: Leukapheresis · Procedure: Magnetic Resonance Imaging · Drug: Melphalan · Procedure: Multigated Acquisition Scan · Radiation: Radiation Therapy · Procedure: Radionuclide Imaging · Other: Survey Administration · Drug: Temozolomide · Drug: Thiotepa · Drug: Topotecan · Procedure: Tumor Resection · Drug: Vincristine
See detailed description
Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Drug: Carboplatin · Drug: Cisplatin · Procedure: Computed Tomography · Drug: Cyclophosphamide · Biological: Dinutuximab · Drug: Doxorubicin · Procedure: Echocardiography Test · Drug: Etoposide · Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan · Procedure: Hematopoietic Cell Transplantation · Drug: Irinotecan · Drug: Isotretinoin · Procedure: Leukapheresis · Procedure: Magnetic Resonance Imaging · Drug: Melphalan · Procedure: Multigated Acquisition Scan · Radiation: Radiation Therapy · Procedure: Radionuclide Imaging · Other: Survey Administration · Drug: Temozolomide · Drug: Thiotepa · Drug: Topotecan · Procedure: Tumor Resection · Drug: Vincristine
Undergo blood and urine sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Given IV
Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Given IV
Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin
Undergo CT scan
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Frindovyx, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719
Given IV
Also known as: Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18, monoclonal antibody Ch14.18, Qarziba, Unituxin
Given IV
Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Undergo ECHO
Also known as: EC, Echocardiography
Given IV
Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213
Undergo FDG PET
Also known as: FDG PET/CT
Undergo stem cell infusion
Also known as: HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation, HSCT, SCT, Stem Cell Transplant, stem cell transplantation, Stem Cell Transplantation, NOS
Given IV
Given PO
Also known as: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid, 13-cRA, Absorica, Accure, Accutane, Amnesteem, cis-Retinoic Acid, Cistane, Claravis, Isotretinoinum, Isotrex, Isotrexin, Myorisan, Neovitamin A, Neovitamin A Acid, Oratane, Retinoicacid-13-cis, Ro 4-3780, Ro-4-3780, Roaccutan, Roaccutane, Roacutan, Sotret, ZENATANE
Undergo apheresis
Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Given IV
Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalan for Injection-Hepatic Delivery System, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813
Undergo MUGA
Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning
Undergo radiation therapy
Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Undergo I-MIBG scan
Also known as: Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, Scintigraphy
Ancillary studies
Given PO or via NG or G tube
Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ
Given IV
Also known as: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa, SH 105, SH-105, SH105, STEPA, Tepadina, Tepylute, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312
Given IV
Also known as: Hycamptamine, Topotecan Lactone
Undergo tumor resection surgery
Given IV
Also known as: LCR, Leurocristine, VCR, Vincrystine
Event free survival (EFS)
EFS time is calculated from time of randomization to Arms A or B to first episode of disease relapse or progression, second malignancy, or death, or until last contact if no event has occurred.
Time frame: Up to 3 years
End of Induction (EOI) response rate
The response rate will be calculated among all evaluable patients at end of Induction. Responders are defined as patients who achieve a \>= partial response per the revised 2017 International Neuroblastoma Response Criteria (INRC)
Time frame: From randomization to end of extended Induction, up to 12 months
Overall survival (OS)
OS time is calculated from time of randomization to Arms A or B until death, or until last contact if patient is alive.
Time frame: Up to 3 years
Incidence of adverse events
The proportion of patients with at least one grade 3 or higher non-hematologic toxicity or grade 4 or higher hematologic toxicity during protocol therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, will be reported.
Time frame: Up to 2 years
GD2 expression
Dinutuximab binding to pre-therapy patient tumor samples will be measured and categorized as high or low.
Time frame: Up to 12 months
Association between tumor and host factors and outcomes
A series of univariate and multivariate Cox proportional hazards (for EFS and OS) and logistic regression (for responders vs. non-responders) models will be fit for patients in Arms A and B to evaluate the relationship between tumor and host factors (including tumor ALK and other somatic mutations, copy-number aberrations, gene fusions, gene expression, and pathogenic germline variants) and chemo-immunotherapy during Induction with outcome.
Time frame: Up to 10 years
Circulating biomarkers and markers of minimal residual disease
Will be assessed by comparing the proportion of patients with detectable vs. non-detectable tumor markers (including circulating tumor deoxyribonucleic acid, circulating free DNA, circulating tumor cells, and immune function profiling) between Arms A and B during and after induction and post-consolidation therapy using chi-squared tests at each individual time point, and Cochran's Q across time points to determine if there is a consistent difference in proportions between arms across time. In addition, the tumor markers will be analyzed as continuous variables using longitudinal data analysis methodology such as mixed effects models or generalized estimating equations as appropriate.
Time frame: Up to 10 years
Patterns of failure
The impact of early or late chemoimmunotherapy during Induction on the probability of the involvement of a specific disease site at first relapse will be evaluated using Fisher's exact test.
Time frame: Up to 10 years
Effect of telomere maintenance mechanisms
A series of univariate and multivariate Cox proportional hazards (for EFS and OS) and logistic regression (for responders vs. non-responders) models will be fit for patients in arms A and B to evaluate the relationship between telomere maintenance mechanism and chemoimmunotherapy during Induction with outcome. Patients will be classified into 3 groups by telomere maintenance mechanism (TMM) based on messenger ribonucleic acid expression of TERT and analysis of telomeric DNA C-circles: telomerase (TERT) positive, alternative of lengthening of telomeres (ALT) positive, or no identified TMM.
Time frame: Up to 10 years
Functional and quality of life outcomes
Will descriptively summarize and compare the total Memorial Symptom Assessment Scale scores, total sub-domain scores, and individual symptom scores between patients randomized to receive dinutuximab during Induction (Arm B) to those of patients randomized to standard Induction (Arm A).
Time frame: At serial time points during Induction, Extended Induction, Post-Consolidation, and at the end of therapy
Adequacy of diagnostic biopsy specimens
Will be evaluated by descriptively comparing the successful delineation of histologic classification, MYCN amplification status, and ALK status via the traditional method of obtaining tissue for diagnosis, open surgical biopsy, versus the less invasive percutaneous core needle biopsy.
Time frame: At time of tissue collection
Associations between family-reported adverse social determinants of health and both clinical outcomes and biology
Kaplan-Meier curves of EFS and OS will be generated and used to calculate 3-year EFS and OS estimates. Associations between social determinants of health (SDOH) and survival outcomes and time to receipt of dinutuximab will be evaluated with univariate and multivariate Cox proportional hazard models. Log-binomial regression will be used to estimate risk ratios and 95% CI for the occurrence of dinutuximab consent to randomization and therapy receipt by SDOH exposure. Effect modification of outcomes as a function of poverty, stratified by race/ethnicity, will be explored.
Time frame: Up to 10 years
Develop and validate deep learning predictors of Induction response (imaging objective)
Scans will be given as input to a convolutional neural network trained to predict EOI response.
Time frame: At diagnosis, EOI, during Extended Induction, and end of Extended Induction
Compare institutional versus central determination of overall response, individual response components, and PEIR and GEIR determination (imaging objective)
Will be assessed by calculating the percentage of patients receiving the same EOI institutional and centrally reviewed determination of overall response, individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease), and PEIR and GEIR. In addition, Cohen's kappa will be calculated to evaluate the concordance in each of these response measures.
Time frame: Up to 10 years
Incidence of late toxicities
Will be addressed by calculating the proportion of treated patients with each late effect, including but not limited to impaired organ function, neuropsychiatric toxicity, and secondary malignancy. A 95% confidence interval will be placed on each proportion.
Time frame: Up to 10 years
Reduced dose radiotherapy to the primary site clinical target volume (CTV) in patients with complete response of the primary site at EOI results in comparable local control relative to historical cohorts
The cumulative incidence of local progression (CILP) in patients with complete response of the primary site at EOI and GEIR on this study will be compared to the CILP rate of 11.2±1.8% observed on ANBL0532 using Gray's test.
Time frame: Up to 10 years
Post-transplant complications
Will be evaluated by calculating the incidence of endothelial injury complications and non-relapse mortality within 100 days of transplant, transplant-associated thrombotic microangiopathy (TA-TMA), severe TA-TMA, and sinusoidal obstruction syndrome (SOS) on Arms A and B and comparing between arms with a chi-squared test. The impact of TA-TMA occurrence on the timing or exclusion of subsequent therapy and interventions utilized to treat the TA-TMA, and associations with outcomes (EFS and OS) will be assessed.
Time frame: Up to 100 days post-transplant
Associations between end of induction (EOI) response and individual response components
Log-rank tests will be used to explore the association between EOI response (using both the revised INRC and GEIR/PEIR classification) and individual response components (primary tumor, soft tissue and bone metastatic disease, and bone marrow metastatic disease) with outcome (EFS and OS).
Time frame: Up to 10 years
Changes in image-defined risk factors (IDRF)
The proportion of patients in the analytic cohort for whom each particular IDRF and also the presence of any IDRF is absent prior to surgical resection will be computed. McNemar's test for paired observations will be applied to determine whether there is a difference in the proportion of each IDRF and any IDRF present before and after initial therapy, and conditional logistic regression will be used to compare between treatment arms A and B. The IDRF status after initial therapy and whether there has been a change from diagnosis will be associated with surgical outcome (complete vs. incomplete resection, presence or absence of surgical complications) using chi-squared tests, and compared between treatment arms A and B with the Cochran-Mantel-Haenszel test. The association of IDRF status with presence or absence of local failure after primary tumor resection will also be evaluated using a chi-squared test, and compared between treatment arms A and B with the Cochran-Mantel-Haenszel.
Time frame: Up to 10 years
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Plan to share: Yes — "NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."
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Studies of the drug tested here: Dinutuximab
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