NeuroblastomaPhase 1NCT03332667
MIBG With Dinutuximab +/- Vorinostat
A Phase 1 study testing 131I-MIBG, Dinutuximab and Vorinostat in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 12 sites in United States.
Trial summary
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- 131I-MIBG, Dinutuximab and Vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 12 sitesUnited States
- Study dates
- 12 Sep 2018to 23 Feb 2024
- Phase
- Phase 1
- 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 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must have evidence of MIBG uptake into tumor at ≥ 1 site (bone or soft tissue) within 28 days prior to study entry and subsequent to any intervening therapy.
- Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
- Patients must have a history of high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate-risk, but then reclassified as high-risk are also eligible.
- All patients must have at least one of the following
- Recurrent/progressive disease: after the diagnosis of high risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy
- No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma b1) Refractory disease- a best overall response of no response/stable disease since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
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- b2) Persistent disease- a best overall response of no partial response since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
- Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):
- For recurrent/progressive or refractory disease, at least one MIBG avid bone site.
- For persistent disease, if a patient has 3 or more MIBG avid lesions, then no biopsy is required. If a patients has only 1 or 2 MIBG avid bone lesion sites then biopsy confirmation of neuroblastoma or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required to be obtained at any time point prior to enrollment.
- For MIBG non-avid tumors, patients must have at least one FDG avid site and a biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment from at least one FDG-avid site.
- Any amount of neuroblastoma tumor cells in the bone marrow done at the time of study enrollment based on routine morphology with or without immunocytochemistry in at least one sample from bilateral aspirates and biopsies.
- At least one soft tissue lesion that meets criteria for a TARGET lesion as defined by:
- SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for lymph nodes ≥ 15 mm on short axis. Lesions meeting size criteria will be considered measurable.
- In addition to size, a lesion needs to meet one of the following criteria except for patients with parenchymal CNS lesions which only need to meet size criteria: b1) MIBG avid. For patients with recurrent/progressive or refractory disease, no biopsy is required. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions sites, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at time of enrollment is required to be obtained. If a patient has 3 or more MIBG avid lesions, then no biopsy is required.
- b2) MIBG non avid tumors: Patients must have at least one FDG avid site and biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment.
- At least one non-target soft tissue lesion that is not measurable, but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma or is MIBG avid at any time prior to enrollment.
- Patients must have a life expectancy of at least 12 weeks and a Lansky (≤16 years) or Karnofsky (>16 years) score of at least 50.
- Prior Therapy 1. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration.
- 2. Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows:
- 1. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration.
- 2. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration.
- 3. Monoclonal antibodies: must have received last dose at least 7 days or 3 half-lives whichever is longer, but no longer than 30 days (with recovery of any associated toxicities), prior to protocol therapy.
- 4. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities.
- 5. Radiation: must not have received small port radiation within 7 days prior to registration.
- 6. Hematopoietic Stem Cell Transplant: 7. IVIG 8. Therapeutic MIBG 9. Investigational medicines covered under another IND 10. Medications interfering with MIBG uptake 11. Medications that prolong QTc (Part B only) 12. Valproic acid (Part B only) 11) All patients must have adequate organ function defined as:
- Hematological Function:
- Absolute Phagocyte count (APC= neutrophils and monocytes): ≥ 1000/µL
- Absolute Neutrophil count: ≥750/µL
- Absolute Lymphocyte count ≥ 500/µL
- Platelet count: ≥ 50,000/µL, transfusion independent (no platelet transfusions within 1 week)
- Hemoglobin ≥ 10 g/dL (may transfuse)
- Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria above.
- Renal Function: Age-adjusted serum creatinine ≤ to 1.5 x normal for age/gender OR creatinine clearance or GFR greater than or equal to 60 cc/min/1.73m2
- Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND SGPT (ALT) 135 and SGOT (AST) ≤ 3 x upper limit of normal. Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving clinically
- Cardiac Function: Normal ejection fraction documented by either echocardiogram or radionuclide MUGA evaluation OR Normal fractional shortening documented by echocardiogram
- Pulmonary Function: No dyspnea at rest, no oxygen requirement.
- 12) Reproductive Status: All post-menarchal females must have a negative beta-HCG. Males and females of reproductive age and childbearing potential must use effective contraception for the duration of their participation.
- 13) Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.
- 14) Autologous peripheral blood stem cells (PBSC)•The minimum dose for peripheral blood stem cells is 2.0 x 106viable CD34+ cells/kg. Patients who do not meet this minimum requirement for available PBSCs are not eligible. •Only un-purged stem cells are allowed unless a center has separate FDA approval for infusion of purged stem cells. •For patients whose body weight exceeds ideal body weight (IBW) by more than 20%, adjusted body weight may be used for the calculation of PBSC dose 15) Physician deems that there is reasonable ability to obtain vorinostat via commercial supply (Part B Only)
Who cannot join
- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Patients with disease of any major organ system that would compromise their ability to withstand therapy.
- Patients who have received prior allogeneic stem cell transplant
- Patients who have received prior solid organ transplantation
- Patients must not have received prior total body irradiation
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- Prior HDAC inhibitor given in combination with therapeutic 131I-MIBG(Part B only)
- The maximum total allowable dose of 131I-MIBG that can be given per institutional guidelines must be at least 90% of the calculated 131I-MIBG dose or the patient is not eligible.
- Patients who are on hemodialysis.
- Patients with an active or uncontrolled infection.
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
- Patient declines participation in NANT 2004-05, the NANT Biology Study
- Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation.
- Patients with a history of having to discontinue anti-GD2 antibody therapy due to toxicity are not eligible.
- Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given in combination with therapeutic 131I-MIBG.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
C.S Mott Children's Hospital
Ann Arbor, Michigan, 48109
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, 30322
Children Hospital of Colorado
Aurora, Colorado, 80045
Children's Hospital Boston
Boston, Massachusetts, 02115
University of North Carolina
Chapel Hill, North Carolina, 27599
University of Chicago, Comer Children's Hospital
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Cook Children's Healthcare System
Fort Worth, Texas, 76104
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
About this study
Official title: A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat for Relapsed/Refractory Neuroblastoma
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose level. A 6 patient expansion cohort may then be enrolled.
Read the detailed description
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult studies suggest that radiation can enhance the efficacy of immunotherapy and targeted therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination with dinutuximab and vorinostat aims to determine the recommended phase 2 pediatric dose of these three therapies in combination.
- Conditions
- Neuroblastoma
- Being tested
- 131I-MIBG, Dinutuximab, Vorinostat, Sargramostim, Potassium Iodide
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
131I-MIBGRadiation
Also called 131I-Metaiodobenzylguanidine, Iobenguane sulfate, m-Iodobenzylguanidine sulfate, MIBG
Patients will receive 131I-MIBG on day 1. 131I-MIBG dose will be based on the dose level assigned at the time of patient registration
DinutuximabDrug
Also called Chimeric Monoclonal Antibody 14.18, MAB Ch 14.18, Unituxin, Ch14.18
Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab dose will be based on the dose level assigned at the time of patient registration.
VorinostatDrug
Also called Zolina
Vorinostat will be given on day 0-13. Vorinostat dose will be based on the dose level assigned at the time of patient registration.
SargramostimDrug
Sargramostim (GM-CSF) will be given on day 8-17 at 250 mcg/m^2
Potassium IodideDrug
Potassium iodide will be given by mouth at a dose of 6mg/kg 8-12 hours prior to infusion of 131I-MIBG on Day 1 and then 1mg/kg/dose by mouth starting 4-6 hours after completion of MIBG infusion and continuing every 4 hours on protocol days 1-7 and then 1mg/kg/dose by mouth once daily on protocol days 8-45
| Study group | Role | What they receive |
|---|---|---|
| Cohort A DL1 | Experimental | Patients will receive 131I-MIBG on day 1 at 12 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy Receives: Radiation: 131I-MIBG; Drug: Dinutuximab; Drug: Sargramostim; Drug: Potassium Iodide |
| Cohort A DL2 | Experimental | Patients will receive 131I-MIBG on day 1 at 15 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy Receives: Radiation: 131I-MIBG; Drug: Dinutuximab; Drug: Sargramostim; Drug: Potassium Iodide |
| Cohort A DL3 | Experimental | Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy Receives: Radiation: 131I-MIBG; Drug: Dinutuximab; Drug: Sargramostim; Drug: Potassium Iodide |
| Cohort B DL4 | Experimental | Vorinostat will be given on days 0-13 at 180 mg/m2/dose. Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy Receives: Radiation: 131I-MIBG; Drug: Dinutuximab; Drug: Vorinostat; Drug: Sargramostim; Drug: Potassium Iodide |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD/RP2D Determination Cohort A
Proportion of patients with Course 1 DLT in Cohort A
Measured: All toxicities from enrollment until completion of course 1 (Day 56)
MTD/RP2D Determination Cohort B
Proportion of patients with Course 1 DLT in Cohort B
Measured: All toxicities from enrollment until completion of course 1 (Day 56)
Describe Non-Hematological Toxicities Cohort A
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort A
Measured: All toxicities from enrollment through 30 days following end of protocol therapy, up to 5 months
Describe Non Hematological Toxicities Cohort B
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort B
Measured: All toxicities from enrollment through 30 days following end of protocol therapy, up to 5 months
Secondary outcomes (2)
Overall Response Cohort A
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in Cohort A
Measured: From Day 1 of protocol therapy through 30 days following end of protocol therapy, up to 5 months
Overall Response Cohort B
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in Cohort B
Measured: From Day 1 of protocol therapy through 30 days following end of protocol therapy, up to 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start12 Sep 2018
- Primary completion23 Feb 2024
- Study completion23 Feb 2024
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Approaches to Neuroblastoma Therapy Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- United Therapeutics, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Thomas Cash, MD, Study chair, Children's Healthcare of AtlantaAraz Marachelian, MD, MS, Study director, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332667
- Sponsor's protocol ID
- NANT2017-01
- Other IDs
- 2P01CA217959
- Status last verified
- Mar 2025
- First submitted
- 2 Nov 2017
- Last updated
- 16 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cash T, Marachelian A, DuBois SG, Chi YY, Baregamyan A, Groshen SG, Jonus HC, Shamirian A, Crowley M, Goodarzian F, Acharya PT, Pawel B, Erbe AK, Shahi A, Zaborek J, Kennedy E, Asgharzadeh S, Villablanca JG, Pinto N, Weiss BD, Mosse YP, Desai AV, Macy ME, Granger M, Vo KT, Sondel PM, Matthay KK, Park JR, Goldsmith KC. Phase I Study of 131I-Metaiodobenzylguanidine With Dinutuximab +/- Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial. J Clin Oncol. 2025 Aug;43(22):2490-2501. doi: 10.1200/JCO-24-02612. Epub 2025 Jun 23.
PubMed 40549985
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat for Relapsed/Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT03332667
- Acronym / sponsor ID
- NANT2017-01
- Conditions
- Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- New Approaches to Neuroblastoma Therapy ConsortiumUniversity, hospital or other
- Collaborators
- United Therapeutics, National Cancer Institute (NCI)
- Study start
- 12 Sep 2018 (actual)
- Primary completion
- 23 Feb 2024 (actual)
- Study completion
- 23 Feb 2024 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 16 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial, 131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6 patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose level. A 6 patient expansion cohort may then be enrolled.
Detailed description
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult studies suggest that radiation can enhance the efficacy of immunotherapy and targeted therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination with dinutuximab and vorinostat aims to determine the recommended phase 2 pediatric dose of these three therapies in combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A DL1 | Experimental | Radiation: 131I-MIBG, Drug: Dinutuximab, Drug: Sargramostim, Drug: Potassium IodidePatients will receive 131I-MIBG on day 1 at 12 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy |
| Cohort A DL2 | Experimental | Radiation: 131I-MIBG, Drug: Dinutuximab, Drug: Sargramostim, Drug: Potassium IodidePatients will receive 131I-MIBG on day 1 at 15 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy |
| Cohort A DL3 | Experimental | Radiation: 131I-MIBG, Drug: Dinutuximab, Drug: Sargramostim, Drug: Potassium IodidePatients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy |
| Cohort B DL4 | Experimental | Radiation: 131I-MIBG, Drug: Dinutuximab, Drug: Vorinostat, Drug: Sargramostim, Drug: Potassium IodideVorinostat will be given on days 0-13 at 180 mg/m2/dose. Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (40 listed)
- Patients must have evidence of MIBG uptake into tumor at ≥ 1 site (bone or soft tissue) within 28 days prior to study entry and subsequent to any intervening therapy.
- Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
- Patients must have a history of high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate-risk, but then reclassified as high-risk are also eligible.
- All patients must have at least one of the following
- b2) Persistent disease- a best overall response of no partial response since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
Key exclusion criteria (15 listed)
- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Patients with disease of any major organ system that would compromise their ability to withstand therapy.
- Patients who have received prior allogeneic stem cell transplant
- Patients who have received prior solid organ transplantation
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 |
|---|---|---|
| 131I-MIBGAlso: 131I-Metaiodobenzylguanidine, Iobenguane sulfate, m-Iodobenzylguanidine sulfate, MIBGPatients will receive 131I-MIBG on day 1. 131I-MIBG dose will be based on the dose level assigned at the time of patient registration | Radiation | Cohort A DL1, Cohort A DL2, Cohort A DL3, Cohort B DL4 |
| DinutuximabAlso: Chimeric Monoclonal Antibody 14.18, MAB Ch 14.18, Unituxin, Ch14.18Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab dose will be based on the dose level assigned at the time of patient registration. | Drug | Cohort A DL1, Cohort A DL2, Cohort A DL3, Cohort B DL4 |
| VorinostatAlso: ZolinaVorinostat will be given on day 0-13. Vorinostat dose will be based on the dose level assigned at the time of patient registration. | Drug | Cohort B DL4 |
| SargramostimSargramostim (GM-CSF) will be given on day 8-17 at 250 mcg/m^2 | Drug | Cohort A DL1, Cohort A DL2, Cohort A DL3, Cohort B DL4 |
| Potassium IodidePotassium iodide will be given by mouth at a dose of 6mg/kg 8-12 hours prior to infusion of 131I-MIBG on Day 1 and then 1mg/kg/dose by mouth starting 4-6 hours after completion of MIBG infusion and continuing every 4 hours on protocol days 1-7 and then 1mg/kg/dose by mouth once daily on protocol days 8-45 | Drug | Cohort A DL1, Cohort A DL2, Cohort A DL3, Cohort B DL4 |
Primary outcome
MTD/RP2D Determination Cohort A
Time frame: All toxicities from enrollment until completion of course 1 (Day 56)
Proportion of patients with Course 1 DLT in Cohort A
MTD/RP2D Determination Cohort B
Time frame: All toxicities from enrollment until completion of course 1 (Day 56)
Proportion of patients with Course 1 DLT in Cohort B
Describe Non-Hematological Toxicities Cohort A
Time frame: All toxicities from enrollment through 30 days following end of protocol therapy, up to 5 months
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort A
Describe Non Hematological Toxicities Cohort B
Time frame: All toxicities from enrollment through 30 days following end of protocol therapy, up to 5 months
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort B
2 secondary outcomes
Overall Response Cohort A
Time frame: From Day 1 of protocol therapy through 30 days following end of protocol therapy, up to 5 months
Overall Response Cohort B
Time frame: From Day 1 of protocol therapy through 30 days following end of protocol therapy, up to 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40549985Cash T, Marachelian A, DuBois SG, Chi YY, Baregamyan A, Groshen SG, Jonus HC, Shamirian A, Crowley M, Goodarzian F, Acharya PT, Pawel B, Erbe AK, Shahi A, Zaborek J, Kennedy E, Asgharzadeh S, Villablanca JG, Pinto N, Weiss BD, Mosse YP, Desai AV, Macy ME, Granger M, Vo KT, Sondel PM, Matthay KK, Park JR, Goldsmith KC. Phase I Study of 131I-Metaiodobenzylguanidine With Dinutuximab +/- Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy Trial. J Clin Oncol. 2025 Aug;43(22):2490-2501. doi: 10.1200/JCO-24-02612. Epub 2025 Jun 23.
- Individual participant dataSharing planned: Undecided
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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.
Thomas Cash, MD study chair
Children's Healthcare of Atlanta
Araz Marachelian, MD, MS study director
Children's Hospital Los Angeles
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 131I-MIBG, Dinutuximab and Vorinostat in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 12 sites in United States.
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 40 inclusion and 15 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 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2025). 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?
MTD/RP2D Determination Cohort A (time frame: All toxicities from enrollment until completion of course 1 (Day 56)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03332667, which also lists 1 linked publication.
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 16 Apr 2025; AzTrials last refreshed its copy on 5 Nov 2026.