Evidence map›Paper›PMID 26791869›Full record

Trial reportCancer chemotherapy and pharmacology2016

Comparative pharmacokinetics, safety, and tolerability of two sources of ch14.18 in pediatric patients with high-risk neuroblastoma following myeloablative therapy.

Araz Marachelian, Ami Desai, Frank Balis, Howard Katzenstein, Muna Qayed, Michael Armstrong, Kathleen A Neville, Susan L Cohn, Mark Bush, Rudy Gunawan and 3 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05421897 (RAPID Feasibility Study), which is not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05421897 phase1active not recruitingnot on this mapstarted 2022, after this paper: background citation

RAPID Feasibility Study: A Pilot Study for the Rapid Infusion of Dinutuximab

TypeinterventionalSponsorChildren's Hospital Los AngelesRan2022 to 2026Enrolled11ConditionsNeuroblastomaArmsDinutuximab with Chemotherapy
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Commonly Reported Adverse Events Associated With Pediatric Immunotherapy: A Systematic Review From the Children's Oncology GroupJournal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses
    Pooled it
  3. Trial
  4. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Trial
  5. Article
  6. Immunotherapy with anti-GInternational journal of cancer · 2023
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 11 institutions in 1 country.

Araz MarachelianChildren's Hospital Los Angeles, University of Southern California, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA. amarachelian@chla.usc.edu.
Ami DesaiChildren's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Frank BalisChildren's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Howard KatzensteinVanderbilt University School of Medicine, 2200 Pierce Ave 397 PRB, Nashville, TN, 37232-6310, USA.
Muna QayedAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University School of Medicine, 1405 Clifton Rd NE, Atlanta, GA, 30322, USA.
Michael ArmstrongDuke University, DUMC 102382, Durham, NC, 27710, USA.
Kathleen A NevilleArkansas Children's Hospital/University of Arkansas for Medical Sciences, 1 Children's Way; Slot 512-23, Little Rock, AR, 72202, USA.
Susan L CohnDepartment of Pediatrics, The University of Chicago, 900 E 57th Street, KCBD, Rm 5100, Chicago, IL, 60637, USA.
Mark BushSchool of Pharmacy, Wingate University, 515 N. Main Street, Wingate, NC, 28174, USA.
Rudy GunawanIonis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA, 92010, USA.
Allison Pecha LimUnited Therapeutics Corporation, 55 TW Alexander Drive, Research Triangle Park, NC, 27709, USA.
Malcolm A SmithNational Cancer Institute, 9609 Medical Center Dr, MSC 9739, Bethesda, MD, 20892-9739, USA.
L Mary SmithUnited Therapeutics Corporation, 55 TW Alexander Drive, Research Triangle Park, NC, 27709, USA.
Children's Hospital of Philadelphia · USUnited Therapeutics (United States) · USArkansas Department of Agriculture · USDuke Medical Center · USEmory University · USIonis Pharmaceuticals (United States) · USNational Cancer Institute · USUniversity of Chicago · USUniversity of Southern California · USVanderbilt University · USWingate University · US

Funding

Center for Molecular &Cellular Studies of Ped DiseaseK12HD043494 · NICHD · DUKE UNIVERSITY · PI REED, ANN M. · 2003 to 2017
$5.2M
NICHD NIH HHS K12 HD043494
6 · The paper itself

Abstract

purposeDinutuximab (Unituxin™; ch14.18), a monoclonal antibody against disialoganglioside, improved survival as part of post-consolidation therapy for high-risk neuroblastoma. United Therapeutics Corporation (UTC) assumed ch14.18 production from the National Cancer Institute (NCI); this study evaluates pharmacokinetic comparability, safety, and tolerability of UTC and NCI products.

methodsIn this randomized, two-sequence crossover study, 28 patients aged ≤8 years with high-risk neuroblastoma received equivalent ch14.18-UTC or ch14.18-NCI doses. Despite comparable protein content, nominal doses differed: 17.5 mg/m(2)/day (ch14.18-UTC) and 25 mg/m(2)/day (ch14.18-NCI). Patients received one product during therapy cycles 1 and 2, the other during cycles 3-5. Ch14.18 pharmacokinetic profile characterization used population modeling (NONMEM(®) version 7.2). A two-compartment model with first-order distribution and elimination processes described pharmacokinetic data. Estimated product parameters were normalized to UTC nominal dose. For pharmacokinetic comparability, the final model was used to estimate exposure ratios (UTC/NCI) and associated 90 % confidence intervals (CIs) for area under the curve from time zero to infinity (AUCinf) and maximum concentration (C max). All comparisons were based on a standardized single-dose regimen (17.5 mg/m(2) over 10 h).

resultsFinal-model pharmacokinetic parameters were similar to previously published ch14.18-NCI parameters and comparable for UTC and NCI products. Products' systemic exposures were comparable, with 90 % CIs around ratios for AUCinf (0.96; 90 % CI 0.88-1.04) and C max (1.04; 90 % CI 0.98-1.11) within standard bioequivalence bounds (90 % CI 0.80-1.25). Products' adverse events were similar and consistent with those previously reported.

conclusionsEquivalent actual ch14.18-UTC and ch14.18-NCI doses produced comparable exposures, with no notable safety or tolerability differences.

Indexed as

Antibodies, MonoclonalNeuroblastomaAntineoplastic AgentsChildChild, PreschoolDose-Response Relationship, DrugDrug MonitoringFemaleGangliosidesHumansMaleTreatment OutcomeAntibodies, MonoclonalAntineoplastic AgentsdinutuximabGangliosidessialogangliosidesch14.18DinutuximabPharmacokineticsSafetyTolerabilityUnituxin

Identifiers

PMID26791869
PMCPMC4747995
OpenAlexW2293124958

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.