Rapid Administration Pilot for Infusing Dinutuximab

NCT05421897 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CHLA-22-00205NCI-2025-06180
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Neuroblastoma

Keywords

relapsed neuroblastoma; refractory neuroblastoma; persistent high-risk neuroblastoma; pediatric cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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.

  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.

  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.

  Day 1-126 (or 168 depending on cycle length)

Study Arms (1)

Rapid infusion of dinutuximab with chemotherapy

EXPERIMENTAL

Patients will receive chemotherapy and dinutuximab via rapid infusion

Drug: Dinutuximab with Chemotherapy

Interventions

Dinutuximab with Chemotherapy DRUG

Rapid infusion of dinutuximab in 5 hours or less

Also known as: Cyclophosphamide, Topotecan, Temozolomide, Irinotecan, Sagramostim

Rapid infusion of dinutuximab with chemotherapy

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• I-MIBG therapy: Patients are eligible ≥6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• United Therapeutics: collaborator

Study Sites (7)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Childrens Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's Hospital of Atlanta

Atlanta, Georgia, 30322, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (6)

• 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.

  PMID: 20879881 BACKGROUND

• Yu 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.

  PMID: 33504555 BACKGROUND

• Mody 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.

  PMID: 28549783 BACKGROUND

• Desai 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.

  PMID: 25212536 BACKGROUND

• Marachelian 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.

  PMID: 26791869 BACKGROUND

• Mody 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.

  PMID: 32343642 BACKGROUND

MeSH Terms

Conditions

Neuroblastoma; Neoplasms

Interventions

dinutuximab; Drug Therapy; Cyclophosphamide; Topotecan; Temozolomide; Irinotecan; Colony-Stimulating Factors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Sara-Jane Onyeama, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 16, 2022
• Study Start: November 29, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2029
• Last Updated: September 17, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)