Rapid Administration Pilot for Infusing Dinutuximab

NCT05421897 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CHLA-22-00205NCI-2025-06180
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Studies have shown that the anti-GD2 human-mouse chimeric monoclonal antibody dinutuximab has contributed significantly to the improvement of treatment for children with high-risk neuroblastoma and has become a mainstay in treating high risk neuroblastoma in children as part of up-front therapy and relapsed/refractory therapy. The administration of dinutuximab requires a significant amount of time and resources to complete the 10-20 hour standard infusion time for 4 days in the inpatient setting. During its early development, a phase I study profiling the clinical efficacy and tolerability of dinutuximab infusions in children successfully infused dinutuximab at various rates including over 1 hour at different dose levels. In the adult setting, dinutuximab has been tolerated over substantially shorter infusion times (less than 2 hours). Additionally, another anti-GD2 murine monoclonal antibody naxitamab, which has a similar toxicity profile to dinutuximab, is FDA approved for administration over 90 minutes and is successfully administered in outpatient setting. Given this reassuring data the investigators aim to evaluate the feasibility of the rapid administration of dinutuximab over four hours or less in our patient population of children with high-risk neuroblastoma. The pharmacokinetics, toxicity profile and supportive care requirements will be analyzed and described in order to determine if rapid infusion of dinutuximab can be successfully tolerated over four hours or less which would allow for administration of this agent in the outpatient setting. Should this trial prove to be successful, it would serve to decrease the hospital burden in a positive way by allowing for administration of this immunotherapy agent in the outpatient setting and patients may prefer shorter infusion duration. Furthermore, it could lessen overall costs and inpatient admissions for patients.

Conditions

Neuroblastoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Determine feasibility of administering dinutuximab in Cycle 1

  The number of dinutuximab days tolerated in 4 hours or less in Cycle 1 will be measured

  Day 1 of therapy until Day 21

• Determine average dinutuximab infusion time in Cycle 1

  The infusion time of dinutuximab days administered on Days 1-4 will be measured and the average infusion time will be calculated for each dinutuximab day during Cycle 1.

  Day 1 of therapy until Day 21

Secondary Outcomes (2)

• Determine feasibility of administering Dinutuximab in Cycle 2-6 in 4 hrs or less

  Day 22 of study therapy until Day 126

• Determine average dinutuximab infusion time in Cycles 2-6

  Day 22 of study therapy until Day 126

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 timeframes 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).
• 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. However, they must be held during protocol therapy. The anti-cancer agent may be resumed after completion of final dinutuximab day in each cycle per physician discretion.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Immnoglobulins: IVIG should not be given within 2 weeks of starting dinutuximab treatment and 1 week after completing dinutuximab therapy.
• Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment.
• 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 1 week prior to enrollment if clinically indicated. Palliative radiation while on study is permitted but not during 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 (1)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, 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 1
• 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: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: January 29, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)