Evidence map›Paper›PMID 27292104›Full record

Trial reportThe New England journal of medicine2016

Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.

Hagop M Kantarjian, Daniel J DeAngelo, Matthias Stelljes, Giovanni Martinelli, Michaela Liedtke, Wendy Stock, Nicola Gökbuget, Susan O'Brien, Kongming Wang, Tao Wang and 4 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIComparative StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 669 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
669citing papers in PubMed, 3 pooled it
132.2field-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.

NCT01564784 phase3completednot on this map

An open-label, randomized phase 3 study of inotuzumab ozogamicin compared to a defined investigator's choice in adult patients with relapsed or refractory cd22-positive acute lymphoblastic leukemia (all)

TypeinterventionalSponsorPfizerRan2012 to 2017Enrolled326ConditionsAcute Lymphoblastic LeukemiaArmsinotuzumab ozogamicin, FLAG (fludarabine, cytarabine and G-CSF), HIDAC (high dose cytarabine), cytarabine and mitoxantrone
NCT06554626 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

The Regimen of Blinatumomab and Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating Precursor B Cell Acute Lymphoblastic Leukemia: A Phase II, Single Arm and Multicenter Study

TypeinterventionalSponsorFirst Affiliated Hospital of Zhejiang UniversityRan2024 to 2027Enrolled20ConditionsPrecursor B-Cell Lymphoblastic LeukemiaArmsDexamethasone, Blinatumomab, Venetoclax, Inotuzumab ozogamicin, Methotrexate
3 · Its place in the literature

Who cites it

669 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,340 citations in OpenAlex.

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  13. Flow Cytometric Immunophenotyping of Acute Lymphoblastic Leukemia.Methods in molecular biology (Clifton, N.J.) · 2027
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609 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 10 institutions in 5 countries.

Hagop M KantarjianFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Daniel J DeAngeloFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Matthias StelljesFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Giovanni MartinelliFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Michaela LiedtkeFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Wendy StockFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Nicola GökbugetFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Susan O'BrienFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Kongming WangFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Tao WangFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
M Luisa PaccagnellaFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Barbara SleightFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Erik VandendriesFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Anjali S AdvaniFrom the University of Texas MD Anderson Cancer Center, Houston (H.M.K.); the Dana-Farber Cancer Institute, Boston (D.J.D.), and Pfizer, Cambridge (E.V.) - both in Massachusetts; Universitätsklinikum Münster, Münster (M.S.), and Goethe University, Frankfurt (N.G.) - both in Germany; Institute Seràgnoli, DIMES (Department of Experimental, Diagnostic and Specialty Medicine), University of Bologna, Bologna, Italy (G.M.); Stanford Cancer Institute, Stanford (M.L.), and the University of California, Irvine Medical Center, Orange (S.O.) - both in California; the University of Chicago, Chicago (W.S.); Pfizer, Pearl River, NY (K.W.); Pfizer, Groton, CT (T.W., M.L.P., B.S.); and Cleveland Clinic, Cleveland (A.S.A.).
Pfizer (United States) · USCancer Institute (WIA) · INCleveland Clinic · USDana-Farber Cancer Institute · USGoethe University Frankfurt · DEThe University of Texas MD Anderson Cancer Center · USUniversity Hospital Münster · DEUniversity of Bologna · ITUniversity of California, Irvine Medical Center · USUniversity of Chicago · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

backgroundThe prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy.

methodsIn this phase 3 trial, we randomly assigned adults with relapsed or refractory acute lymphoblastic leukemia to receive either inotuzumab ozogamicin (inotuzumab ozogamicin group) or standard intensive chemotherapy (standard-therapy group). The primary end points were complete remission (including complete remission with incomplete hematologic recovery) and overall survival.

resultsOf the 326 patients who underwent randomization, the first 218 (109 in each group) were included in the primary intention-to-treat analysis of complete remission. The rate of complete remission was significantly higher in the inotuzumab ozogamicin group than in the standard-therapy group (80.7% [95% confidence interval {CI}, 72.1 to 87.7] vs. 29.4% [95% CI, 21.0 to 38.8], P<0.001). Among the patients who had complete remission, a higher percentage in the inotuzumab ozogamicin group had results below the threshold for minimal residual disease (0.01% marrow blasts) (78.4% vs. 28.1%, P<0.001); the duration of remission was longer in the inotuzumab ozogamicin group (median, 4.6 months [95% CI, 3.9 to 5.4] vs. 3.1 months [95% CI, 1.4 to 4.9]; hazard ratio, 0.55 [95% CI, 0.31 to 0.96]; P=0.03). In the survival analysis, which included all 326 patients, progression-free survival was significantly longer in the inotuzumab ozogamicin group (median, 5.0 months [95% CI, 3.7 to 5.6] vs. 1.8 months [95% CI, 1.5 to 2.2]; hazard ratio, 0.45 [97.5% CI, 0.34 to 0.61]; P<0.001); the median overall survival was 7.7 months (95% CI, 6.0 to 9.2) versus 6.7 months (95% CI, 4.9 to 8.3), and the hazard ratio was 0.77 (97.5% CI, 0.58 to 1.03) (P=0.04). In the safety population, the most frequent grade 3 or higher nonhematologic adverse events with inotuzumab ozogamicin were liver-related. Veno-occlusive liver disease of any grade occurred in 15 patients (11%) who received inotuzumab ozogamicin and in 1 patient (1%) who received standard therapy.

conclusionsThe rate of complete remission was higher with inotuzumab ozogamicin than with standard therapy, and a higher percentage of patients in the inotuzumab ozogamicin group had results below the threshold for minimal residual disease. Both progression-free and overall survival were longer with inotuzumab ozogamicin. Veno-occlusive liver disease was a major adverse event associated with inotuzumab ozogamicin. (Funded by Pfizer; INO-VATE ALL ClinicalTrials.gov number, NCT01564784.).

Indexed as

AdolescentAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansInotuzumab OzogamicinIntention to Treat AnalysisMaleMiddle AgedPrecursor Cell Lymphoblastic Leukemia-LymphomaRemission InductionSialic Acid Binding Ig-like Lectin 2Survival AnalysisYoung AdultAntibodies, Monoclonal, HumanizedCD22 protein, humanInotuzumab OzogamicinSialic Acid Binding Ig-like Lectin 2

Identifiers

PMID27292104
PMCPMC5594743
OpenAlexW2419639370

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

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.