Evidence map›Paper›PMID 33067614›Full record

ArticleBlood2021

A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study).

Erica Brivio, Franco Locatelli, Marta Lopez-Yurda, Andrea Malone, Cristina Díaz-de-Heredia, Bella Bielorai, Claudia Rossig, Vincent H J van der Velden, Anneke C J Ammerlaan, Adriana Thano and 11 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07476729 (International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group), which is not on this map. Cited by 61 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 3 pooled it
10.3field-weighted citation impact, top 1% 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.

NCT07476729 phase3not yet recruitingnot on this mapstarted 2026, after this paper: background citation

International Study for Treatment of Childhood Relapsed Precursor B-Cell ALL 2020 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group

TypeinterventionalSponsorCharite University, Berlin, GermanyRan2026 to 2033Enrolled750ConditionsB-Cell Acute Lymphoblastic LeukaemiaArmsInotuzumab ozogamicin (INO), Blinatumomab
3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 3 syntheses or guidelines pooled it, 88 citations in OpenAlex.

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  13. Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 15 institutions in 11 countries.

Erica BrivioPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Franco LocatelliDepartment of Pediatric Hematology/Oncology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome, Rome, Italy.
Marta Lopez-YurdaPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Andrea MaloneChildren's Health Ireland at Crumlin, Dublin, Ireland.
Cristina Díaz-de-HerediaDepartment of Pediatric Hematology and Oncology, University Hospital Vall d'Hebron, Barcelona, Spain.
Bella BieloraiDepartment of Pediatric Hematology-Oncology, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
Claudia RossigDepartment of Pediatric Hematology and Oncology, University Children's Hospital Münster, Germany.
Vincent H J van der VeldenDepartment of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Anneke C J AmmerlaanPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Adriana ThanoPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Inge M van der SluisPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Monique L den BoerPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Ying ChenPfizer Global Product Development, San Diego, CA.
Barbara SleightPfizer Inc, Groton, CT.
Benoit BrethonDepartment of Pediatric Hematology, Hôpital Robert-Debré, Assistance Publique-Hôpitaux de Paris, Paris, France.
Karsten NysomDepartment of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Rigshospitalet, Copenhagen, Denmark.
Lucie SramkovaDepartment of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
Ingrid ØraDepartment of Pediatric Oncology and Hematology, Childhood Cancer Research Unit, Lund University Hospital, Lund, Sweden.
Luciana VintiDepartment of Pediatric Hematology/Oncology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, Sapienza University of Rome, Rome, Italy.
Christiane Chen-SantelDepartment of Pediatrics, Division of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany; and.
Christian Michel ZwaanPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Princess Máxima Center · NLBambino Gesù Children's Hospital · ITPfizer (United States) · USThe Netherlands Cancer Institute · NLAssistance Publique – Hôpitaux de Paris · FRCharles University · CZChildren's Health Ireland at Crumlin · IEErasmus MC · NLKarolinska University Hospital · SEOncode Institute · NLRigshospitalet · DKSheba Medical Center · ILUniversitätsmedizin Rostock · DEUniversity Hospital Münster · DEVall d'Hebron Hospital Universitari · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This phase 1 study investigated the recommended phase 2 dose (RP2D) of inotuzumab ozogamicin (InO), a CD22-directed antibody-drug conjugate, in pediatric patients with multiple relapsed/refractory (R/R) CD22+ acute lymphoblastic leukemia (ALL). Patients (age ≥1 year or <18 years) received 3 doses of InO (days 1, 8, and 15) per course. Dose escalation was based on dose-limiting toxicities (DLTs) during course 1. Dose level 1 (DL1) was 1.4 mg/m2 (0.6, 0.4, 0.4 mg/m2) and DL2 was 1.8 mg/m2 (0.8, 0.5, 0.5 mg/m2). Secondary end points included safety, antileukemic activity, and pharmacokinetics. Twenty-five patients (23 evaluable for DLTs) were enrolled. In course 1, the first cohort had 1 of 6 (DL1) and 2 of 5 (DL2) patients who experienced DLTs; subsequent review considered DL2 DLTs to be non-dose-limiting. Dose was de-escalated to DL1 while awaiting protocol amendment to re-evaluate DL2 in a second cohort, in which 0 of 6 (DL1) and 1 of 6 (DL2) patients had a DLT. Twenty-three patients experienced grade 3 to 4 adverse events; hepatic sinusoidal obstruction syndrome was reported in 2 patients after subsequent chemotherapy. Overall response rate after course 1 was 80% (95% confidence interval [CI], 59% to 93%) (20 of 25 patients; DL1: 75% [95% CI, 43% to 95%], DL2: 85% [95% CI, 55% to 98%]). Of the responders, 84% (95% CI, 60% to 97%) achieved minimal residual disease (MRD)-negative complete response, and 12-month overall survival was 40% (95% CI, 25% to 66%). Nine patients received hematopoietic stem cell transplantation or chimeric antigen receptor T cells after InO. InO median maximum concentrations were comparable to simulated adult concentrations. InO was well tolerated, demonstrating antileukemic activity in heavily pretreated children with CD22+ R/R ALL. RP2D was established as 1.8 mg/m2 per course, as in adults. This trial was registered at https://www.clinicaltrialsregister.eu as EUDRA-CT 2016-000227-71.

Indexed as

Antineoplastic Agents, ImmunologicalChildChild, PreschoolFemaleHumansInfantInotuzumab OzogamicinMaleNeoplasm Recurrence, LocalPrecursor Cell Lymphoblastic Leukemia-LymphomaTreatment OutcomeAntineoplastic Agents, ImmunologicalInotuzumab Ozogamicin

Identifiers

PMID33067614
PMCPMC7995290
OpenAlexW3093461422

What OpenQuestion holds

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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.