NeuroblastomaPhase 2RAPIDNCT05421897
Rapid Administration Pilot for Infusing Dinutuximab
A Phase 2 study testing Dinutuximab with Chemotherapy in people with Neuroblastoma, run by Children's Hospital Los Angeles at 7 sites in United States.
Trial summary
Dinutuximab is an immunotherapy that has greatly improved outcomes for children with high-risk neuroblastoma and is now a standard part of treatment for both newly diagnosed and relapsed disease. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Dinutuximab with Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesUnited States
- Study dates
- 29 Nov 2022to Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age: Patients ≥ 12 months of age at the time of enrollment are eligible for this study.
- Diagnosis: Patients must have a diagnosis of relapsed , refractory (defined as achieving less than a partial response), or persistent high-risk neuroblastoma or ganglioneuroblastoma (nodular) [verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites at the time of diagnosis] and have been designated as having high-risk disease based on COG risk classification.
- No minimal sites of disease are required for this study.
- Prior Therapy (all time-frames below apply from time of enrollment):
- Must have completed high-risk Induction therapy with at least 4 cycles of chemotherapy.
- At least 14 days must have elapsed since completion of myelosuppressive therapy.
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- Patients must have received previous treatment with dinutuximab (with or without chemotherapy) within 2 months prior to enrollment without any dose-modifications
- Anti-cancer agents not known to be myelosuppressive (e.g. not associated with substantially reduced platelet or ANC counts) are permitted while on study with PI approval and must be held during dinutuximab therapy and may be resumed after completion of final dinutuximab day in each cycle per physician discretion.
- Monoclonal antibodies: ≥ 7days ( 3 half-lives) from infusion of last dose of antibody and all related toxicity must have resolved to Grade ≤ 1.
- Immunoglobulins: IVIG should not be given within 2 weeks of starting dinutuximab treatment or 1 week after completing dinutuximab therapy.
- Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment and must not require ongoing pharmacologic doses of systemic corticosteroids during protocol therapy.
- Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. (The only exception is for patients known to require 2mg/kg or less of hydrocortisone, or an equivalent dose of an alternative corticosteroid, as premedication for blood product administration in order to avoid allergic transfusion reactions). The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency.
- Radiation may be given up to 7days prior to enrollment if clinically indicated. Palliative radiation while on study is permitted except during dinutuximab infusion days.
- Stem cell transplant must be ≥ 6months prior to enrollment. Patients who received autologous stem cell infusion to support non-myeloablative therapy (such as 131 I-MIBG) are eligible at any time as long as they meet the other criteria for eligibility.
- 131I-MIBG therapy: Patients are eligible ≥6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met.
- Adequate Bone Marrow Function Defined As:
- Peripheral absolute neutrophil count (ANC) ≥750/microL
- Platelet count ≥50,000/mL (transfusion independent for prior 7 days). Exemptions may be granted for patient specific criteria (i.e. low platelet function due to history of extensive prior therapy or bone marrow disease)
- Hematologic growth factor (ie GM-CSF, GCSF or bioequivalent) may given up to 14 days prior to enrollment Note: concurrent use of platelet directed growth factor is permitted
- Adequate Renal Function Defined As:
- Creatinine clearance or radioisotope GFR ≥70mL/min/1.73m2 or
- Adequate serum creatinine based on age/gender
- Note: Patients with history of transplant-associated thrombotic microangiopathy (TA-TMA) must have a creatinine clearance or radioisotope GFR at baseline to assess renal function and must meet the above criteria.
- Adequate Liver Function Defined As:
- Total bilirubin ≤1.5 x ULN for age AND
- SGPT (ALT) ≤ 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45U/L.
- Adequate Central Nervous System Function Defined As:
- Patients with a history of CNS disease must have no clinical evidence of active progressive CNS disease at the time of study enrollment. Patients with history of CNS disease need to have at least stable tumor in the CNS for at least one month.
- Patients with seizure disorders may be enrolled if seizures are well controlled on antiepileptic medication
- CNS toxicity ≤ Grade 2
- Adequate Cardiac Function Defined As:
- Shortening fraction of ≥27% by ECHO, or
- Ejection fraction of ≥50% by ECHO or gated radionuclide study.
- Adequate Pulmonary Function Defined As: No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry >94% if there is a clinical indication for pulse oximetry. For patients who do not have respiratory symptoms, full pulmonary function tests are NOT required.
Who cannot join
- Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study.
- Females of childbearing potential (≥ 10 years of age and /or post-menarchal) must have a negative pregnancy test to be eligible for this study, and they must agree to use 2 acceptable methods of contraception or abstain from heterosexual intercourse while participating in this study.
- Pregnant women will be excluded from this study.
- Female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study.
- Patients with uncontrolled hypertension are not eligible; uncontrolled hypertension is defined as sustained hypertension not well-controlled on blood pressure medication(s).
- If enrolling on Regimen A (temodar, irinotecan, dinutuximab arm only): patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible. Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment are not eligible. Patients must not have ≥ Grade 2 diarrhea
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- Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma.
- Patients must not have uncontrolled infection.
- Patients with a history of Grade 4 allergic reactions to anti-GD2 antibodies or reactions that required permanent discontinuation of the anti-GD2 therapy are not eligible.
- Patients who could not tolerate standard dose of dinutuximab infusion in 20 hour or less are not eligible.
- Patients with a significant intercurrent illness or disease of any major organ system that would impair their ability to withstand protocol therapy are not eligible
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Hospital of Atlanta
Atlanta, Georgia, 30322
Childrens Hospital of Colorado
Aurora, Colorado, 80045
University of Texas Southwestern
Dallas, Texas, 75390
Cook Children's Medical Center
Fort Worth, Texas, 76104
Childrens Hospital Los Angeles
Los Angeles, California, 90027
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
About this study
Official title: RAPID Study: A Pilot Study for the Rapid Infusion of Dinutuximab
Dinutuximab is an immunotherapy that has greatly improved outcomes for children with high-risk neuroblastoma and is now a standard part of treatment for both newly diagnosed and relapsed disease. However, the medication is typically given through an intravenous (IV) infusion over 10-20 hours a day for four consecutive days, requiring prolonged hospital stays that place a significant burden on children, families, and healthcare resources.
Earlier studies of dinutuximab, as well as experience with a similar immunotherapy, suggest that these medications can be safely given over a much shorter period of time.
Read more
This study is evaluating whether children with high-risk neuroblastoma can safely receive dinutuximab over five hours or less. Early results have been encouraging. The first group of patients successfully received most treatments with dinutuximab in about two hours. Children experienced very low pain levels and required approximately 78% less opioid pain medication compared with the traditional longer infusion. Several patients were able to receive treatment as outpatients without requiring hospital admission, while hospitalizations that did occur were primarily related to chemotherapy or other non-medical reasons rather than the rapid infusion itself.
The study is now expanded to further evaluate the safety of rapid infusion across multiple treatment cycles at different centers in the United States. Researchers will also examine how the drug is processed by the body, whether the immune system develops antibodies against the treatment, and whether the faster infusion continues to reduce the need for opioid pain medication. In addition, children and their caregivers will complete questionnaires about symptoms and treatment experiences to better understand the impact of the faster dinutuximab infusion on quality of life and the overall treatment experience.
Read the detailed description
Neuroblastoma is the most common extra-cranial solid tumor of childhood. While it comprises only 8% of all childhood cancer cases, neuroblastoma is responsible for 12% of cancer deaths in children under 15 years of age. Approximately 50% of neuroblastoma patients are classified as high-risk, and over half of these children succumb to their disease despite intensive multi-modal therapy. The prognosis is worse for patients whose disease is refractory to initial therapy or who experience a recurrence of their tumor, as the majority of these patients cannot be cured of their disease. However, rates of event free survival and overall survival have improved over the past decades with the introduction of dinutuximab.
Dinutuximab is a chimeric monoclonal antibody that targets disialoganglioside (GD2) receptors. It has become an integral modality in the treatment of high-risk neuroblastoma (HR NBL) in up-front therapy and in the setting of relapsed or refractory disease. Additionally, there are numerous ongoing trials that include dinutuximab as part of the backbone therapy or in combination with other agents to improve tumor response in HR NBL patients.
A limiting factor for the use of dinutuximab has been the management of infusion-related toxicities. GD2 is expressed on neurons, skin melanocytes, and peripheral pain fibers of human tissues, which is evident in the common manifestation of pain during infusions. Other most common adverse effects include hypotension, capillary leak syndrome, and infusion-related reactions. These toxicities typically last during the standardized infusion duration of 10-20 hours but typically do not correlate with plasma levels. Pain that occurs during the infusion typically resolves shortly after the infusion is completed, despite the fact that dinutuximab persists in the circulation, which suggests that pain may be related to infusion rate rather than drug exposure (AUC). Due to the lengthy infusion duration and high frequency of side effects, dinutuximab infusions currently require significant hospital resources including nursing care, opioid infusions, around the clock supportive care medications, and a hospital stay for a minimum of 4-5 days.
With the expectation of repeated cycles of dinutuximab for different protocols in HR NBL treatment and with the expansion of dinutuximab studies in other GD2 positive tumors, there is a need to improve the administration and management of dinutuximab for future practicality and patient durability. A different anti-GD2 antibody naxitamab with a similar side effect profile to dinutuximab has been FDA approved for administration in the outpatient setting. Therefore, there is potential for dinutuximab to be administered in the outpatient setting. Although some studies have attempted to modify the administration of dinutuximab dosing and infusion durations, none have focused on shortening infusion time in the pediatric setting.
Dinutuximab was shown to significantly improve survival in children with HR NBL when administered after dose-intensive combination chemotherapy and high-dose myeloablative therapy with autologous stem cell rescue, and when combined with immunomodulating agents sargramostim and aldesleukin (IL-2) in the randomized phase 3 clinical trial, ANBL 0032. This Children's Oncology Group (COG) trial found that the combination of dinutuximab with sargramostim and IL-2 enhanced antibody-dependent cell-mediated cytotoxicity when given with isotretinoin in post-consolidation therapy. The addition of immunotherapy to isotretinoin in the post-consolidation phase was found to be significantly superior to isotretinoin alone. This led to the FDA approval of dinutuximab in the post-consolidation setting of neuroblastoma therapy. More recently, when dinutuximab was combined with irinotecan, temozolomide and sargramostim in patients with relapsed/refractory neuroblastoma (ANBL 1221) improved response rates were seen and as a result, this regimen is now considered first line for patients with relapsed or refractory disease in North America.
In 2019, the COG Neuroblastoma Committee released a memo removing IL-2 from the standard care for post-consolidation immunotherapy in HR NBL patients. The memo cited the data from two studies by the International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) that showed no difference in survival outcomes with the inclusion of IL-2. This led to IL-2 elimination from both SIOPEN and COG protocols. Ongoing trials of post-consolidation immunotherapy were adopted to reflect this update but there are no completed clinical trials reporting data of dinutuximab with sargramostim without chemotherapy or IL-2.
The current dose of dinutuximab is 17.5mg/m2/day given over 10 hours for 4 days. It is typically given with pre-medications, opiates and supportive care with careful monitoring of AE's and early intervention as needed. The infusion rate may be slowed down but needs to be completed in 20 hours. Since the published results of dinutuximab efficacy in neuroblastoma and with many years of experience administering it, patients have been successfully completing many courses of therapy in the relapsed setting with good control of AE's.
Initially the A0935A protocol directed dinutuximab infusion over 10 hours but was then revised to be given over 5 hours based on tolerability. The ANBL 0032 protocol directed the infusion of dinutuximab over 6 hours. This was suspended temporarily in 2009 for an investigation into the apparent increase in allergy-like AEs related to IL-2; the protocol was amended to extend the dinutuximab infusion duration to 10-20 hours. However since IL-2 removal from standard protocols in 2019, no studies have evaluated the tolerability of infusing dinutuximab in under 10 hours in the HR NBL patient population.
Based on clinical experience of infusing this agent at Children's Hospital Los Angeles (CHLA), the peak time for capillary leak and worsening pain occurs at or after 4 hours of dinutuximab infusing. Therefore, it is reasonable to conclude that fast infusion may ameliorate some of the symptoms experienced by patients.
Although dinutuximab has most recently been given in 10-20 hour infusions based on the ANBL0032 study data that included IL-2, the experience of the early studies of dinutuximab with shorter infusion rates, and the fact that similar anti-GD2 antibodies such as Naxitamab and Hu14.18k322A, are well tolerated in 4 hours or less, support further investigation into decreasing the infusion time of dinutuximab in pediatric patients. Our pilot study has shown that the administration of rapid dinutuximab infusion is feasible. Expansion to a multi-institutional study will provide the safety data needed to support broader implementation of this approach and facilitate its incorporation into future clinical trials, with the ultimate goal of improving the delivery of dinutuximab therapy.
- Conditions
- Neuroblastoma
- Being tested
- Dinutuximab with Chemotherapy
- Keywords
- relapsed neuroblastoma, refractory neuroblastoma, persistent high-risk neuroblastoma, pediatric cancer
- Medical subject headings
- Neuroblastoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dinutuximab with ChemotherapyDrug
Also called Cyclophosphamide, Topotecan, Temozolomide, Irinotecan
Rapid infusion of dinutuximab in 5 hours or less
| Study group | Role | What they receive |
|---|---|---|
| Rapid infusion of dinutuximab with chemotherapy | Experimental | Patients will receive chemotherapy and dinutuximab via rapid infusion Receives: Drug: Dinutuximab with Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility Cohort Primary Aim #1: To determine the feasibility of administering rapid dinutuximab infusion in 5 hours or less on dinutuximab infusion days 1-4 in cycle 1
Feasibility will be defined as receiving at least one day of dinutuximab infusion in 5 hours or less without unacceptable toxicity in cycle 1. The proportion of patients successfully receiving at least one day of dinutuximab infusion in 5 hours or less will be documented for each of the two treatment groups with the 95% confidence interval to quantify variability.
Measured: Day 1 of therapy until Day 21 (or 28)
Feasibility Cohort Primary Aim #2: To determine the average dinutuximab infusion time on dinutuximab infusion days 1-4 in cycle 1
The average dinutuximab infusion time will be computed across the 4 dinutuximab infusion days in cycle 1, along with the standard error to describe the variability.
Measured: Day 1 of therapy until Day 21 (or 28)
Feasibility Cohort + Safety Expansion Cohort Primary Aim #1: To determine the safety and tolerability of administering rapid dinutuximab infusion in 5 hours or less for all cycles
The frequency of unacceptable toxicities in patients, the frequency of patient coming off study due to toxicity or treatment-related deaths will be tabulated. In addition, The incidence of all treatment-related toxicities and grade 3 or higher toxicities in aggregate will be reported.
Measured: Day 1-126 (or 168 depending on cycle length)
Secondary outcomes (3)
Feasibility Cohort Secondary Aim #1: To determine the feasibility of administering rapid dinutuximab infusion in 5 hours or less on dinutuximab infusion days 1-4 in subsequent cycles.
The proportion of patients successfully receiving at least one day of dinutuximab infusion in 5 hours or less in subsequent cycles will be documented for each of the two groups with the 95% confidence interval to quantify variability
Measured: Day 22 (or 28) of study therapy until Day 121 or 168 (depending on cycle length)
Feasibility Cohort Secondary Aim #2: To determine the average dinutuximab infusion time on dinutuximab days 1-4 in subsequent cycles.
The average dinutuximab infusion time will be computed across the 4 dinutuximab infusion days in subsequent cycles, along with the standard error to describe the variability.
Measured: Day 22 (or 28) of study therapy until Day 121 or 168
Feasibility Cohort + Safety Expansion Cohort Secondary Aim #1: To determine the average dinutuximab infusion time on dinutuximab infusion days in all cycles.
The average dinutuximab infusion time across the 4 dinutuximab infusion days by cycle and in all cycles in aggregate, along with the standard error to describe the variability
Measured: Day 1-126 (or 168 depending on cycle length)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2022
- Study start29 Nov 2022
- Primary completionNov 2028 (estimated)
- Study completionNov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- United Therapeutics
- Responsible party
- Principal investigator, Sara-Jane Onyeama, Children's Hospital Los Angeles
- Investigators
- Sara-Jane Onyeama, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05421897
- Sponsor's protocol ID
- CHLA-22-00205
- Other IDs
- NCI-2025-06180
- Acronym
- RAPID
- Status last verified
- Oct 2025
- First submitted
- 8 Jun 2022
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123.
PubMed 20879881Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, Hank JA, Batova A, London WB, Tenney SC, Smith M, Shulkin BL, Parisi M, Matthay KK, Cohn SL, Maris JM, Bagatell R, Park JR, Sondel PM. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021 Apr 15;27(8):2179-2189. doi: 10.1158/1078-0432.CCR-20-3909. Epub 2021 Jan 27.
PubMed 33504555Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):946-957. doi: 10.1016/S1470-2045(17)30355-8. Epub 2017 May 23.
PubMed 28549783Desai AV, Fox E, Smith LM, Lim AP, Maris JM, Balis FM. Pharmacokinetics of the chimeric anti-GD2 antibody, ch14.18, in children with high-risk neuroblastoma. Cancer Chemother Pharmacol. 2014 Nov;74(5):1047-55. doi: 10.1007/s00280-014-2575-9. Epub 2014 Sep 12.
PubMed 25212536Marachelian A, Desai A, Balis F, Katzenstein H, Qayed M, Armstrong M, Neville KA, Cohn SL, Bush M, Gunawan R, Lim AP, Smith MA, Smith LM. Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy. Cancer Chemother Pharmacol. 2016 Feb;77(2):405-12. doi: 10.1007/s00280-015-2955-9. Epub 2016 Jan 20.
PubMed 26791869Mody R, Yu AL, Naranjo A, Zhang FF, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Hank JA, Felder M, Birstler J, Sondel PM, Asgharzadeh S, Glade-Bender J, Katzenstein H, Maris JM, Park JR, Bagatell R. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 1;38(19):2160-2169. doi: 10.1200/JCO.20.00203. Epub 2020 Apr 28.
PubMed 32343642
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RAPID Study: A Pilot Study for the Rapid Infusion of Dinutuximab
- ClinicalTrials.gov ID
- NCT05421897
- Acronym / sponsor ID
- RAPID / CHLA-22-00205
- Conditions
- Neuroblastoma
- Keywords
- relapsed neuroblastoma, refractory neuroblastoma, persistent high-risk neuroblastoma, pediatric cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- United Therapeutics
- Study start
- 29 Nov 2022 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2029 (estimated)
- First posted
- 16 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dinutuximab is an immunotherapy that has greatly improved outcomes for children with high-risk neuroblastoma and is now a standard part of treatment for both newly diagnosed and relapsed disease. However, the medication is typically given through an intravenous (IV) infusion over 10-20 hours a day for four consecutive days, requiring prolonged hospital stays that place a significant burden on children, families, and healthcare resources.
Earlier studies of dinutuximab, as well as experience with a similar immunotherapy, suggest that these medications can be safely given over a much shorter period of time.
This study is evaluating whether children with high-risk neuroblastoma can safely receive dinutuximab over five hours or less. Early results have been encouraging. The first group of patients successfully received most treatments with dinutuximab in about two hours. Children experienced very low pain levels and required approximately 78% less opioid pain medication compared with the traditional longer infusion. Several patients were able to receive treatment as outpatients without requiring hospital admission, while hospitalizations that did occur were primarily related to chemotherapy or other non-medical reasons rather than the rapid infusion itself.
The study is now expanded to further evaluate the safety of rapid infusion across multiple treatment cycles at different centers in the United States. Researchers will also examine how the drug is processed by the body, whether the immune system develops antibodies against the treatment, and whether the faster infusion continues to reduce the need for opioid pain medication. In addition, children and their caregivers will complete questionnaires about symptoms and treatment experiences to better understand the impact of the faster dinutuximab infusion on quality of life and the overall treatment experience.
Detailed description
Neuroblastoma is the most common extra-cranial solid tumor of childhood. While it comprises only 8% of all childhood cancer cases, neuroblastoma is responsible for 12% of cancer deaths in children under 15 years of age. Approximately 50% of neuroblastoma patients are classified as high-risk, and over half of these children succumb to their disease despite intensive multi-modal therapy. The prognosis is worse for patients whose disease is refractory to initial therapy or who experience a recurrence of their tumor, as the majority of these patients cannot be cured of their disease. However, rates of event free survival and overall survival have improved over the past decades with the introduction of dinutuximab.
Dinutuximab is a chimeric monoclonal antibody that targets disialoganglioside (GD2) receptors. It has become an integral modality in the treatment of high-risk neuroblastoma (HR NBL) in up-front therapy and in the setting of relapsed or refractory disease. Additionally, there are numerous ongoing trials that include dinutuximab as part of the backbone therapy or in combination with other agents to improve tumor response in HR NBL patients.
A limiting factor for the use of dinutuximab has been the management of infusion-related toxicities. GD2 is expressed on neurons, skin melanocytes, and peripheral pain fibers of human tissues, which is evident in the common manifestation of pain during infusions. Other most common adverse effects include hypotension, capillary leak syndrome, and infusion-related reactions. These toxicities typically last during the standardized infusion duration of 10-20 hours but typically do not correlate with plasma levels. Pain that occurs during the infusion typically resolves shortly after the infusion is completed, despite the fact that dinutuximab persists in the circulation, which suggests that pain may be related to infusion rate rather than drug exposure (AUC). Due to the lengthy infusion duration and high frequency of side effects, dinutuximab infusions currently require significant hospital resources including nursing care, opioid infusions, around the clock supportive care medications, and a hospital stay for a minimum of 4-5 days.
With the expectation of repeated cycles of dinutuximab for different protocols in HR NBL treatment and with the expansion of dinutuximab studies in other GD2 positive tumors, there is a need to improve the administration and management of dinutuximab for future practicality and patient durability. A different anti-GD2 antibody naxitamab with a similar side effect profile to dinutuximab has been FDA approved for administration in the outpatient setting. Therefore, there is potential for dinutuximab to be administered in the outpatient setting. Although some studies have attempted to modify the administration of dinutuximab dosing and infusion durations, none have focused on shortening infusion time in the pediatric setting.
Dinutuximab was shown to significantly improve survival in children with HR NBL when administered after dose-intensive combination chemotherapy and high-dose myeloablative therapy with autologous stem cell rescue, and when combined with immunomodulating agents sargramostim and aldesleukin (IL-2) in the randomized phase 3 clinical trial, ANBL 0032. This Children's Oncology Group (COG) trial found that the combination of dinutuximab with sargramostim and IL-2 enhanced antibody-dependent cell-mediated cytotoxicity when given with isotretinoin in post-consolidation therapy. The addition of immunotherapy to isotretinoin in the post-consolidation phase was found to be significantly superior to isotretinoin alone. This led to the FDA approval of dinutuximab in the post-consolidation setting of neuroblastoma therapy. More recently, when dinutuximab was combined with irinotecan, temozolomide and sargramostim in patients with relapsed/refractory neuroblastoma (ANBL 1221) improved response rates were seen and as a result, this regimen is now considered first line for patients with relapsed or refractory disease in North America.
In 2019, the COG Neuroblastoma Committee released a memo removing IL-2 from the standard care for post-consolidation immunotherapy in HR NBL patients. The memo cited the data from two studies by the International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN) that showed no difference in survival outcomes with the inclusion of IL-2. This led to IL-2 elimination from both SIOPEN and COG protocols. Ongoing trials of post-consolidation immunotherapy were adopted to reflect this update but there are no completed clinical trials reporting data of dinutuximab with sargramostim without chemotherapy or IL-2.
The current dose of dinutuximab is 17.5mg/m2/day given over 10 hours for 4 days. It is typically given with pre-medications, opiates and supportive care with careful monitoring of AE's and early intervention as needed. The infusion rate may be slowed down but needs to be completed in 20 hours. Since the published results of dinutuximab efficacy in neuroblastoma and with many years of experience administering it, patients have been successfully completing many courses of therapy in the relapsed setting with good control of AE's.
Initially the A0935A protocol directed dinutuximab infusion over 10 hours but was then revised to be given over 5 hours based on tolerability. The ANBL 0032 protocol directed the infusion of dinutuximab over 6 hours. This was suspended temporarily in 2009 for an investigation into the apparent increase in allergy-like AEs related to IL-2; the protocol was amended to extend the dinutuximab infusion duration to 10-20 hours. However since IL-2 removal from standard protocols in 2019, no studies have evaluated the tolerability of infusing dinutuximab in under 10 hours in the HR NBL patient population.
Based on clinical experience of infusing this agent at Children's Hospital Los Angeles (CHLA), the peak time for capillary leak and worsening pain occurs at or after 4 hours of dinutuximab infusing. Therefore, it is reasonable to conclude that fast infusion may ameliorate some of the symptoms experienced by patients.
Although dinutuximab has most recently been given in 10-20 hour infusions based on the ANBL0032 study data that included IL-2, the experience of the early studies of dinutuximab with shorter infusion rates, and the fact that similar anti-GD2 antibodies such as Naxitamab and Hu14.18k322A, are well tolerated in 4 hours or less, support further investigation into decreasing the infusion time of dinutuximab in pediatric patients. Our pilot study has shown that the administration of rapid dinutuximab infusion is feasible. Expansion to a multi-institutional study will provide the safety data needed to support broader implementation of this approach and facilitate its incorporation into future clinical trials, with the ultimate goal of improving the delivery of dinutuximab therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rapid infusion of dinutuximab with chemotherapy | Experimental | Drug: Dinutuximab with ChemotherapyPatients will receive chemotherapy and dinutuximab via rapid infusion |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (34 listed)
- Age: Patients ≥ 12 months of age at the time of enrollment are eligible for this study.
- Diagnosis: Patients must have a diagnosis of relapsed , refractory (defined as achieving less than a partial response), or persistent high-risk neuroblastoma or ganglioneuroblastoma (nodular) [verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites at the time of diagnosis] and have been designated as having high-risk disease based on COG risk classification.
- No minimal sites of disease are required for this study.
- Must have completed high-risk Induction therapy with at least 4 cycles of chemotherapy.
- At least 14 days must have elapsed since completion of myelosuppressive therapy.
Key exclusion criteria (11 listed)
- Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study.
- Females of childbearing potential (≥ 10 years of age and /or post-menarchal) must have a negative pregnancy test to be eligible for this study, and they must agree to use 2 acceptable methods of contraception or abstain from heterosexual intercourse while participating in this study.
- Pregnant women will be excluded from this study.
- Female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study.
- Patients with uncontrolled hypertension are not eligible; uncontrolled hypertension is defined as sustained hypertension not well-controlled on blood pressure medication(s).
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 |
|---|---|---|
| Dinutuximab with ChemotherapyAlso: Cyclophosphamide, Topotecan, Temozolomide, IrinotecanRapid infusion of dinutuximab in 5 hours or less | Drug | Rapid infusion of dinutuximab with chemotherapy |
Primary outcome
Feasibility Cohort Primary Aim #1: To determine the feasibility of administering rapid dinutuximab infusion in 5 hours or less on dinutuximab infusion days 1-4 in cycle 1
Time frame: Day 1 of therapy until Day 21 (or 28)
Feasibility will be defined as receiving at least one day of dinutuximab infusion in 5 hours or less without unacceptable toxicity in cycle 1. The proportion of patients successfully receiving at least one day of dinutuximab infusion in 5 hours or less will be documented for each of the two treatment groups with the 95% confidence interval to quantify variability.
Feasibility Cohort Primary Aim #2: To determine the average dinutuximab infusion time on dinutuximab infusion days 1-4 in cycle 1
Time frame: Day 1 of therapy until Day 21 (or 28)
The average dinutuximab infusion time will be computed across the 4 dinutuximab infusion days in cycle 1, along with the standard error to describe the variability.
Feasibility Cohort + Safety Expansion Cohort Primary Aim #1: To determine the safety and tolerability of administering rapid dinutuximab infusion in 5 hours or less for all cycles
Time frame: Day 1-126 (or 168 depending on cycle length)
The frequency of unacceptable toxicities in patients, the frequency of patient coming off study due to toxicity or treatment-related deaths will be tabulated. In addition, The incidence of all treatment-related toxicities and grade 3 or higher toxicities in aggregate will be reported.
3 secondary outcomes
Feasibility Cohort Secondary Aim #1: To determine the feasibility of administering rapid dinutuximab infusion in 5 hours or less on dinutuximab infusion days 1-4 in subsequent cycles.
Time frame: Day 22 (or 28) of study therapy until Day 121 or 168 (depending on cycle length)
Feasibility Cohort Secondary Aim #2: To determine the average dinutuximab infusion time on dinutuximab days 1-4 in subsequent cycles.
Time frame: Day 22 (or 28) of study therapy until Day 121 or 168
Feasibility Cohort + Safety Expansion Cohort Secondary Aim #1: To determine the average dinutuximab infusion time on dinutuximab infusion days in all cycles.
Time frame: Day 1-126 (or 168 depending on cycle length)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Background: PubMed 20879881Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. doi: 10.1056/NEJMoa0911123.
- Background: PubMed 33504555Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, Hank JA, Batova A, London WB, Tenney SC, Smith M, Shulkin BL, Parisi M, Matthay KK, Cohn SL, Maris JM, Bagatell R, Park JR, Sondel PM. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021 Apr 15;27(8):2179-2189. doi: 10.1158/1078-0432.CCR-20-3909. Epub 2021 Jan 27.
- Background: PubMed 28549783Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):946-957. doi: 10.1016/S1470-2045(17)30355-8. Epub 2017 May 23.
- Background: PubMed 25212536Desai AV, Fox E, Smith LM, Lim AP, Maris JM, Balis FM. Pharmacokinetics of the chimeric anti-GD2 antibody, ch14.18, in children with high-risk neuroblastoma. Cancer Chemother Pharmacol. 2014 Nov;74(5):1047-55. doi: 10.1007/s00280-014-2575-9. Epub 2014 Sep 12.
- Background: PubMed 26791869Marachelian A, Desai A, Balis F, Katzenstein H, Qayed M, Armstrong M, Neville KA, Cohn SL, Bush M, Gunawan R, Lim AP, Smith MA, Smith LM. Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy. Cancer Chemother Pharmacol. 2016 Feb;77(2):405-12. doi: 10.1007/s00280-015-2955-9. Epub 2016 Jan 20.
- Background: PubMed 32343642Mody R, Yu AL, Naranjo A, Zhang FF, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Hank JA, Felder M, Birstler J, Sondel PM, Asgharzadeh S, Glade-Bender J, Katzenstein H, Maris JM, Park JR, Bagatell R. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 1;38(19):2160-2169. doi: 10.1200/JCO.20.00203. Epub 2020 Apr 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sara-Jane Onyeama, MD principal investigator
Children's Hospital Los Angeles
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dinutuximab with Chemotherapy in people with Neuroblastoma, run by Children's Hospital Los Angeles at 7 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 34 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
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?
Feasibility Cohort Primary Aim #1: To determine the feasibility of administering rapid dinutuximab infusion in 5 hours or less on dinutuximab infusion days 1-4 in cycle 1 (time frame: Day 1 of therapy until Day 21 (or 28)). The study lists 3 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 NCT05421897, which also lists 6 linked publications.
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 17 Sep 2026.