GanglioneuroblastomaPhase 2NCT03786783
Dinutuximab, Sargramostim, and Combination Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin in people with Ganglioneuroblastoma and High Risk Neuroblastoma, run by National Cancer Institute (NCI) at 10 sites in 3 countries.
Trial summary
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Ganglioneuroblastoma, High Risk Neuroblastoma
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 4 Mar 2019to 31 Mar 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.
- Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. The following disease groups are eligible:
- Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
- MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features; OR
- Age > 547 days regardless of biologic features;
- Patients with INRG stage MS disease with MYCN amplification
Show all 28Show fewer
- Patients with INRG stage L2 disease with MYCN amplification
- Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progress to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M.
- Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M.
- Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing as described).
- Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible.
- Patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
- Creatinine clearance (CrCl) or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
- Age 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
- Age 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
- Age 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
- Age 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
- Age 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
- Age 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
- Age 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
- Age >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL) (within 7 days prior to enrollment).
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN. For the purposes of this study, ULN for ALT is 45 IU/L (within 7 days prior to enrollment).
- Shortening fraction of >= 27% by echocardiogram (within 7 days prior to enrollment).
- Ejection fraction of >= 50% by echocardiogram or radionuclide angiogram (within 7 days prior to enrollment).
- No known contraindication to peripheral blood stem cell (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.
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Who cannot join
- Patients >18 months of age with INRG stage L2, MYCN non-amplified, regardless of additional biologic features.
- Patients with bone marrow failure syndromes.
- Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1) are not eligible.
- Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine, corticosteroids for reasons other than prevention/treatment of allergic reactions, adrenal replacement therapy, etc.) are not eligible.
- Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method during study therapy and for two months after the last dose of ch14.18 (dinutuximab) are not eligible.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States7 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Children's Hospital Los Angeles
Los Angeles, California, 90027
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Australia2 sites
Royal Children's Hospital
Parkville, Victoria, 3052
The Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
Official title: A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Sargramostim helps the body produce normal infection-fighting white blood cells. These cells also help the dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better than combination chemotherapy alone in treating patients with high-risk neuroblastoma.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the feasibility and tolerability of administering ch14.18 (dinutuximab) and sargramostim (GM-CSF) in combination with a multi-agent chemotherapy regimen during cycles 3-5 of the Induction phase for patients with newly-diagnosed high-risk neuroblastoma.
SECONDARY OBJECTIVE:
- To describe the response rates, event-free survival (EFS) and overall survival (OS) for patients receiving the combination of standard Induction chemotherapy and ch14.18 (dinutuximab) followed by tandem transplant, radiation therapy, and post-consolidation immunotherapy.
EXPLORATORY OBJECTIVES:
- To describe the clinical relevance of naturally occurring anti-glycan antibodies in patients receiving ch14.18 (dinutuximab).
II. To describe the clinical relevance of natural killer (NK) receptor NKp30 isoforms in patients receiving ch14.18 (dinutuximab).
III. To describe the association between host factors, including human anti-chimeric antibodies (HACA), and response to protocol therapy.
IV. To describe the immune environment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) during and following treatment.
- To describe the association between levels of circulating GD2, and tumor cell GD2 expression with response to therapy.
OUTLINE:
INDUCTION CYCLES 1-2 (21 days): Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
INDUCTION CYCLE 3: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2 hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) on day 6 or 7 of a 21-day cycle.
INDUCTION CYCLE 4: Patients receive vincristine IV over 1 minute on day 1, doxorubicin IV over 1-15 minutes on days 1-2, cyclophosphamide IV over 1 hour on days 1-2, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.
INDUCTION CYCLE 5: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2 hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.
Patients may undergo surgery after the fourth or fifth cycle of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at the end of Induction proceed to Consolidation. Consolidation treatment begins between 4 and 6 weeks from the start date of Induction chemotherapy cycle 5. For patients who have surgical resection delayed until after Induction chemotherapy cycle 5, Consolidation starts within 4 weeks from the date of surgery.
CONSOLIDATION #1: Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2. Patients then undergo autologous stem cell transplant (ASCT) on day 0.
CONSOLIDATION #2: Patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin IV over 24 hours on days -7 to -4. Patients then undergo ASCT on day 0.
RADIATION THERAPY: Beginning 42-80 days following Consolidation #2, patients receive external beam radiation therapy (EBRT) daily for up to 20 days.
Patients then receive post-Consolidation therapy starting at least 1 week following radiation therapy.
POST-CONSOLIDATION CYCLES 1-5: Patients receive sargramostim SC on days 1-14, dinutuximab IV over 10-20 hours on days 4-7, and isotretinoin orally (PO) twice daily (BID) on days 11-24. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
POST-CONSOLIDATION CYCLE 6: Patients receive isotretinoin PO BID on days 15-28 of a 28-day cycle.
After completion of study treatment, patients are followed up at months 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60.
- Conditions
- Ganglioneuroblastoma, High Risk Neuroblastoma
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Carboplatin, Cisplatin, Cyclophosphamide, Dexrazoxane
- Medical subject headings
- Ganglioneuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant
Undergo ASCT
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
DexrazoxaneDrug
Also called 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI), 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI), ADR 529, ADR-529
Given IV
DinutuximabBiological
Also called Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18
Given IV
DoxorubicinDrug
Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
External Beam Radiation TherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy
Undergo EBRT
IsotretinoinDrug
Also called 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid
Given PO
MelphalanDrug
Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard
Given IV
SargramostimBiological
Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine
Given SC
ThiotepaDrug
Also called 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa
Given IV
TopotecanDrug
Also called Hycamptamine, Topotecan Lactone
Given IV
VincristineDrug
Also called LCR, Leurocristine, VCR, Vincrystine
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) | Experimental | See Detailed Description Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carboplatin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Dexrazoxane; Biological: Dinutuximab; Drug: Doxorubicin; Drug: Etoposide; Radiation: External Beam Radiation Therapy; Drug: Isotretinoin; Drug: Melphalan; Biological: Sargramostim; Drug: Thiotepa; Drug: Topotecan; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Unacceptable Toxicity
Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
Measured: Up to the first 5 cycles of treatment
Percentage of Participants Who Are Feasibility "Failure"
Feasibility "failures" were defined as patients that did not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
Measured: Up to the first 5 cycles of treatment
Secondary outcomes (3)
Response Rate
Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD.
Measured: Up to the first 5 cycles of treatment
Event-free Survival
Per the revised INRC, progressive disease is: 1) > 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬> increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with > 20% increase in longest diameter, taking as reference the smallest sum on study, and with > 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬> 1.2, 8) Bone marrow without tumor infiltration that becomes >5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by > 2-fold and has > 20% tumor infiltration on reassessment.
Measured: Up to 1 year
Overall Survival
Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start4 Mar 2019
- Primary completion31 Dec 2021
- Study completion31 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GanglioneuroblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sara M Federico, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786783
- Sponsor's protocol ID
- NCI-2018-03732
- Other IDs
- NCI-2018-03732, ANBL17P1, ANBL17P1, U10CA180886
- Status last verified
- May 2026
- First submitted
- 24 Dec 2018
- Last updated
- 2 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT03786783
- Acronym / sponsor ID
- NCI-2018-03732
- Conditions
- Ganglioneuroblastoma, High Risk Neuroblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 4 Mar 2019 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Mar 2026 (actual)
- First posted
- 26 Dec 2018 (actual)
- Results
- Posted 14 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II pilot trial studies the side effects and how well dinutuximab and sargramostim work when combined with chemotherapy in patients with high-risk neuroblastoma. Immunotherapy with monoclonal antibodies, such as dinutuximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Sargramostim helps the body produce normal infection-fighting white blood cells. These cells also help the dinutuximab work better. Giving chemotherapy before a stem cell transplant, with drugs such as cisplatin, etoposide, vincristine, doxorubicin, cyclophosphamide, thiotepa, melphalan, etoposide, carboplatin, topotecan, and isotretinoin, helps kill cancer cells that are in the body and helps make room in a patient's bone marrow for new blood-forming cells (stem cells). Giving dinutuximab and sargramostim with combination chemotherapy may work better than combination chemotherapy alone in treating patients with high-risk neuroblastoma.
Detailed description
PRIMARY OBJECTIVE:
- To assess the feasibility and tolerability of administering ch14.18 (dinutuximab) and sargramostim (GM-CSF) in combination with a multi-agent chemotherapy regimen during cycles 3-5 of the Induction phase for patients with newly-diagnosed high-risk neuroblastoma.
SECONDARY OBJECTIVE:
- To describe the response rates, event-free survival (EFS) and overall survival (OS) for patients receiving the combination of standard Induction chemotherapy and ch14.18 (dinutuximab) followed by tandem transplant, radiation therapy, and post-consolidation immunotherapy.
EXPLORATORY OBJECTIVES:
- To describe the clinical relevance of naturally occurring anti-glycan antibodies in patients receiving ch14.18 (dinutuximab).
II. To describe the clinical relevance of natural killer (NK) receptor NKp30 isoforms in patients receiving ch14.18 (dinutuximab).
III. To describe the association between host factors, including human anti-chimeric antibodies (HACA), and response to protocol therapy.
IV. To describe the immune environment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) during and following treatment.
- To describe the association between levels of circulating GD2, and tumor cell GD2 expression with response to therapy.
OUTLINE:
INDUCTION CYCLES 1-2 (21 days): Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity.
INDUCTION CYCLE 3: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2 hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) on day 6 or 7 of a 21-day cycle.
INDUCTION CYCLE 4: Patients receive vincristine IV over 1 minute on day 1, doxorubicin IV over 1-15 minutes on days 1-2, cyclophosphamide IV over 1 hour on days 1-2, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.
INDUCTION CYCLE 5: Patients receive cisplatin IV over 1 hour on days 1-3, etoposide IV over 2 hours on days 1-3, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim SC on day 6 or 7 of a 21-day cycle.
Patients may undergo surgery after the fourth or fifth cycle of Induction at the discretion of treating doctor. Patients with stable disease or better tumor response at the end of Induction proceed to Consolidation. Consolidation treatment begins between 4 and 6 weeks from the start date of Induction chemotherapy cycle 5. For patients who have surgical resection delayed until after Induction chemotherapy cycle 5, Consolidation starts within 4 weeks from the date of surgery.
CONSOLIDATION #1: Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1 hour on days -5 to -2. Patients then undergo autologous stem cell transplant (ASCT) on day 0.
CONSOLIDATION #2: Patients receive melphalan IV over 30 minutes on days -7 to -5, etoposide IV over 24 hours on days -7 to -4, and carboplatin IV over 24 hours on days -7 to -4. Patients then undergo ASCT on day 0.
RADIATION THERAPY: Beginning 42-80 days following Consolidation #2, patients receive external beam radiation therapy (EBRT) daily for up to 20 days.
Patients then receive post-Consolidation therapy starting at least 1 week following radiation therapy.
POST-CONSOLIDATION CYCLES 1-5: Patients receive sargramostim SC on days 1-14, dinutuximab IV over 10-20 hours on days 4-7, and isotretinoin orally (PO) twice daily (BID) on days 11-24. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
POST-CONSOLIDATION CYCLE 6: Patients receive isotretinoin PO BID on days 15-28 of a 28-day cycle.
After completion of study treatment, patients are followed up at months 3, 6, 9, 12, 15, 18, 24, 30, 36, 42, 48, 54, and 60.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) | Experimental | Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Carboplatin, Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Dexrazoxane, Biological: Dinutuximab, Drug: Doxorubicin, Drug: Etoposide, Radiation: External Beam Radiation Therapy, Drug: Isotretinoin, Drug: Melphalan, Biological: Sargramostim, Drug: Thiotepa, Drug: Topotecan, Drug: VincristineSee Detailed Description |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- Patients must be enrolled on ANBL00B1 or APEC14B1 prior to enrollment on ANBL17P1.
- Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites. The following disease groups are eligible:
- Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing as described).
- Patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible.
- Patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible.
Key exclusion criteria (7 listed)
- Patients >18 months of age with INRG stage L2, MYCN non-amplified, regardless of additional biologic features.
- Patients with bone marrow failure syndromes.
- Patients that are >= 12 and =< 18 months of age with INRG stage M and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and deoxyribonucleic acid [DNA] index > 1) are not eligible.
- Patients on immunosuppressive medications (e.g. tacrolimus, cyclosporine, corticosteroids for reasons other than prevention/treatment of allergic reactions, adrenal replacement therapy, etc.) are not eligible.
- Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
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 |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAlso: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell TransplantUndergo ASCT | Procedure or surgery | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518Given IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| DexrazoxaneAlso: 2, 6-Piperazinedione, 4,4'-propylenedi-, (P)- (8CI), 2,6-Piperazinedione, 4, 4'-(1-methyl-1,2-ethanediyl)bis-, (S)- (9CI), ADR 529, ADR-529Given IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| DinutuximabAlso: Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18Given IV | Biological | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| DoxorubicinAlso: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| EtoposideAlso: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, ToposarGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| External Beam Radiation TherapyAlso: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam RadiotherapyUndergo EBRT | Radiation | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| IsotretinoinAlso: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A AcidGiven PO | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| MelphalanAlso: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine MustardGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| SargramostimAlso: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, ProkineGiven SC | Biological | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| ThiotepaAlso: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, OncotiotepaGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| TopotecanAlso: Hycamptamine, Topotecan LactoneGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
| VincristineAlso: LCR, Leurocristine, VCR, VincrystineGiven IV | Drug | Treatment(chemotherapy, dinutuximab, sargramostim, ASCT, EBRT) |
Primary outcome
Percentage of Participants With Unacceptable Toxicity
Time frame: Up to the first 5 cycles of treatment
Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval.
Percentage of Participants Who Are Feasibility "Failure"
Time frame: Up to the first 5 cycles of treatment
Feasibility "failures" were defined as patients that did not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility "failure" rate together with a 95% confidence interval.
3 secondary outcomes
Response Rate
Time frame: Up to the first 5 cycles of treatment
Event-free Survival
Time frame: Up to 1 year
Overall Survival
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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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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. This study is not recruiting at the moment.
Sara M Federico principal investigator
Children's Oncology Group
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Carboplatin and Cisplatin in people with Ganglioneuroblastoma and High Risk Neuroblastoma, run by National Cancer Institute (NCI) at 10 sites in 3 countries.
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 28 inclusion and 7 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: finished, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia, New Zealand. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Unacceptable Toxicity (time frame: Up to the first 5 cycles of treatment). The study lists 2 primary outcomes in all. 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 2 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.