Evidence map›Paper›PMID 24881631›Full record

Trial reportThe New England journal of medicine2014

Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.

John C Byrd, Jennifer R Brown, Susan O'Brien, Jacqueline C Barrientos, Neil E Kay, Nishitha M Reddy, Steven Coutre, Constantine S Tam, Stephen P Mulligan, Ulrich Jaeger and 26 more

7 registry-linked trialsAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 7 registered trials, which are not on this map. Cited by 774 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
774citing papers in PubMed, 8 pooled it
–field-weighted citation impact
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.

NCT01578707 phase3completednot on this map

A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

TypeinterventionalSponsorPharmacyclics LLC.Ran2012 to 2018Enrolled391ConditionsRelapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic LymphomaArmsofatumumab, ibrutinib
NCT03469895 unknown statusnot on this mapstarted 2017, after this paper: background citation

Efficacy of BCR Inhibitors in the Treatment of Autoimmune Cytopenias Associated With Chronic Lymphocytic Leukemia (CLL): A Retrospective Analysis of the French Innovative Leukemia Organization (FILO)

TypeobservationalSponsorInstitut Paoli-CalmettesRan2017 to 2018Enrolled40ConditionsAutoimmune Cytopenia Associated With Chronic Lymphocytic LeukemiaArmsibrutinib ou idelalisib
NCT03689894 phase1 / phase2terminatednot on this mapstarted 2019, after this paper: background citation

Combination Ibrutinib and Rituximab for the Treatment of Chronic Graft-Versus-Host Disease Following Allogeneic Stem Cell Transplant

TypeinterventionalSponsorDartmouth-Hitchcock Medical CenterRan2019 to 2021Enrolled2ConditionsChronic Graft-versus-host-diseaseArmsIbrutinib, Rituximab
NCT03751410 completednot on this mapstarted 2018, after this paper: background citation

Long-term Effect of Chronic Ibrutinib Therapy on Left Atrial Function

Typeobservational_patient_registrySponsorUniversity Hospital Sestre MilosrdniceRan2018 to 2023Enrolled40ConditionsAtrium, Beat, Echocardiography, Physiology
NCT03755947 phase2completednot on this mapstarted 2018, after this paper: background citation

Sequential Triple Therapy With Ibrutinib, Obinutuzumab and Venetoclax in First and Second Line for Patients With Chronic Lymphocytic Leukemia

TypeinterventionalSponsorGrupo Cooperativo de Hemopatías MalignasRan2018 to 2021Enrolled3ConditionsB-Cell Chronic Lymphocytic Leukemia, B-Cell Chronic Lymphocytic Leukemia in Relapse (Diagnosis)ArmsIbrutinib, Obinutuzumab, Venetoclax
NCT04178798 phase3completednot on this mapstarted 2019, after this paper: background citation

Phase III Randomized Study to Investigate the Use of Acalabrutinib in the Treatment of Patients With Early Stage CLL With High Risk of Early Disease Progression

TypeinterventionalSponsorPETHEMA FoundationRan2019 to 2024Enrolled22ConditionsChronic Lymphocytic Leukemia- Binet Staging SystemArmsAcalabrutinib 100 MG Oral Capsule
NCT04734470 unknown statusnot on this mapstarted 2021, after this paper: background citation

Expression of CD19 Complex in Lymphoproliferative Disorders

TypeobservationalSponsorAssiut UniversityRan2021 to 2023Enrolled92ConditionsLymphoproliferative DisordersArmsFlow cytometry
3 · Its place in the literature

Who cites it

774 citing papers in PubMed, 8 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Article
  19. Review
  20. Review

714 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

36 authors.

John C ByrdThe authors' affiliations are listed in the Appendix.
Jennifer R Brown
Susan O'Brien
Jacqueline C Barrientos
Neil E Kay
Nishitha M Reddy
Steven Coutre
Constantine S Tam
Stephen P Mulligan
Ulrich Jaeger
Steve Devereux
Paul M Barr
Richard R Furman
Thomas J Kipps
Florence Cymbalista
Christopher Pocock
Patrick Thornton
Federico Caligaris-Cappio
Tadeusz Robak
Julio Delgado
Stephen J Schuster
Marco Montillo
Anna Schuh
Sven de Vos
Devinder Gill
Adrian Bloor
Claire Dearden
Carol Moreno
Jeffrey J Jones
Alvina D Chu
Maria Fardis
Jesse McGreivy
Fong Clow
Danelle F James
Peter Hillmen
RESONATE Investigators

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
TWO SIGNAL REQUIREMENT FOR NATURAL KILLER IMMUNITYP01CA095426 · NCI · OHIO STATE UNIVERSITY · PI CALIGIURI, MICHAEL A · 2002 to 2016
$29.6M
SPORE Leukemia Tissue BankP50CA140158 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D · 2009 to 2013
$11.2M
Targeted Therapy for Lymphoid MalignanciesR01CA177292 · NCI · OHIO STATE UNIVERSITY · PI ROGERS, KERRY ANNE, WOYACH, JENNIFER A. · 2013 to 2025
$5.3M
Molecular Evaluation of Targeted Therapies in Lymphoid MalignanciesR01CA183444 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C., WOYACH, JENNIFER A. · 2014 to 2018
$2.6M
NCI NIH HHS P01 CA081534NCI NIH HHS P01 CA095426NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA140158NCI NIH HHS R01 CA177292NCI NIH HHS R01 CA183444
6 · The paper itself

Abstract

backgroundIn patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome.

methodsIn this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points.

resultsAt a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P=0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group.

conclusionsIbrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.).

Indexed as

AdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCoughDiarrheaDisease-Free SurvivalFatigueFemaleFollow-Up StudiesHumansLeukemia, Lymphocytic, Chronic, B-CellMaleAdenineAgammaglobulinaemia Tyrosine KinaseAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedibrutinibofatumumabPiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidines

Identifiers

PMID24881631
PMCPMC4134521

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

and 1 more above

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.