Evidence map›Paper›PMID 34162404›Full record

Trial reportJournal of hematology & oncology2021

A precision medicine classification for treatment of acute myeloid leukemia in older patients.

Alice S Mims, Jessica Kohlschmidt, Uma Borate, James S Blachly, Shelley Orwick, Ann-Kathrin Eisfeld, Dimitrios Papaioannou, Deedra Nicolet, Krzysztof Mrόzek, Eytan Stein and 10 more

8 registry-linked trialsAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in Journal of hematology & oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 8 registered trials, which are not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–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.

NCT00003190 phase3completednot on this map

Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With rIL-2 (NSC #373364) vs. No Further Therapy in Previously Untreated Patients With AML >60 Years

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran1998Enrolled640ConditionsAdult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)Armscytarabine, daunorubicin hydrochloride, etoposide, valspodar
NCT00039377 phase2completednot on this map

A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2002 to 2014Enrolled58ConditionsAdult Acute Lymphoblastic Leukemia in RemissionArmsimatinib mesylate, methotrexate, vincristine sulfate, leucovorin calcium, peripheral blood stem cell transplantation
NCT00048958 active not recruitingnot on this map

Cytogenetic Studies in Acute Leukemia and Multiple Myeloma: Companion to CALGB Treatment Studies For Previously Untreated Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM) Patients

TypeobservationalSponsorAlliance for Clinical Trials in OncologyRan1984Enrolled9,000ConditionsAcute Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Multiple MyelomaArmscytogenetic analysis
NCT00085124 phase3completednot on this map

A Phase III Study of Daunorubicin and Cytarabine +/- G3139 (Genasense, Oblimersen Sodium, NSC #683428, IND #58842), a BCL2 Antisense Oligodeoxynucleotide, in Previously Untreated Patients With Acute Myeloid Leukemia (AML) > / = 60 Years

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2003Enrolled500ConditionsAdult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13, q22), Adult Acute Myeloid Leukemia With t(15Armsoblimersen sodium, cytarabine, daunorubicin hydrochloride, laboratory biomarker analysis
NCT00742625 phase1 / phase2completednot on this map

Dose Escalation and Phase II Study of Bortezomib (IND #58443) Added to Standard Daunorubicin and Cytarabine Therapy for Patients With Previously Untreated Acute Myeloid Leukemia Age 60-75 Years

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2008 to 2012Enrolled95ConditionsAcute Myeloid Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)Armsdaunorubicin hydrochloride, cytarabine, bortezomib
NCT00900224 unknown statusnot on this map

Assessment of Novel Molecular Markers in Acute Myeloid Leukemia

TypeobservationalSponsorAlliance for Clinical Trials in OncologyRan2008Enrolled529ConditionsLeukemiaArmsDNA analysis, DNA methylation analysis, gene expression analysis, mutation analysis, polymerase chain reaction
NCT01253070 phase2completednot on this map

A Phase II Study Incorporating Sorafenib (NSC 724772) Into the Therapy of Patients >/= 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2011 to 2021Enrolled54ConditionsAcute Myeloid Leukemia With FLT3/ITD Mutation, Acute Myeloid Leukemia With Inv(16)(p13.1q22) or t(16, 16)(p13.1, q22)ArmsBiopsy, Bone Marrow Aspiration, Cytarabine, Daunorubicin Hydrochloride, Laboratory Biomarker Analysis
NCT01420926 phase2completednot on this map

A Randomized Phase II Trial of Decitabine-Based Induction Strategies for Patients >/= 60 Years Old With Acute Myeloid Leukemia (AML)

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2011 to 2021Enrolled165ConditionsAcute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Therapy-Related Acute Myeloid LeukemiaArmsBortezomib, Decitabine, Laboratory Biomarker Analysis, Pharmacological Study, Quality-of-Life Assessment
3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. 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

20 authors.

Alice S MimsThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA. alice.mims@osumc.edu.ORCID 0000-0002-8971-2199
Jessica KohlschmidtThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Uma BorateThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
James S BlachlyThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Shelley OrwickThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Ann-Kathrin EisfeldThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Dimitrios PapaioannouThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Deedra NicoletThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Krzysztof MrόzekThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Eytan SteinMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Bhavana BhatnagarThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
Richard M StoneDana-Farber/Partners CancerCare, Boston, MA, USA.
Jonathan E KolitzMonter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA.
Eunice S WangRoswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Bayard L PowellWake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA.
Amy BurdThe Leukemia and Lymphoma Society, White Plains, NY, USA.
Ross L LevineMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Brian J DrukerOregon Health and Science University, Portland, OR, USA.
Clara D BloomfieldThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA.
John C ByrdThe Ohio State University Comprehensive Cancer Center, 320 West 10th Avenue, Starling Loving Hall B302, Columbus, OH, 43210, USA. John.Byrd@osumc.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
THE ALLIANCE NCTN BIOREPOSITORY AND BIOSPECIMEN RESOURCEU24CA196171 · NCI · WASHINGTON UNIVERSITY · PI Mine Cicek, Wendy Frankel · 2015 to 2026
$35.0M
SPORE Leukemia Tissue BankP50CA140158 · NCI · OHIO STATE UNIVERSITY · PI MARCUCCI, GUIDO · 2009 to 2013
$11.2M
Network Lead Academic Participating Site: Memorial Sloan Kettering Cancer CenterUG1CA233290 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CAROL AGHAJANIAN, Darren Feldman · 2019 to 2026
$10.2M
OSU as a Network Lead Academic Participating Site for the NCI NCTNUG1CA233331 · NCI · OHIO STATE UNIVERSITY · PI John L. Hays, Dwight H. Owen · 2019 to 2026
$8.9M
NCTN Lead Academic Participating Site at Dana-Farber/Partners Cancer CareUG1CA233180 · NCI · DANA-FARBER CANCER INST · PI Harold John Burstein · 2019 to 2026
$8.6M
ITSC for Leukemia: Novel Molecular strategies for NCTN "Individualized" TherapiesUG1CA233338 · NCI · UNIVERSITY OF CINCINNATI · PI BYRD, JOHN C. · 2019 to 2025
$4.5M
ITSC for Leukemia: Novel Molecular Strategies for NCTN: "Individualized" TherapieU10CA180861 · NCI · OHIO STATE UNIVERSITY · PI BLOOMFIELD, CLARA D, MARCUCCI, GUIDO · 2014 to 2018
$3.4M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016058NCI NIH HHS P50 CA140158NCI NIH HHS R35 CA198183NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180861NCI NIH HHS U10 CA180882NCI NIH HHS U10 CA180888NCI NIH HHS U24 CA196171NCI NIH HHS UG1 CA233180NCI NIH HHS UG1 CA233191NCI NIH HHS UG1 CA233290NCI NIH HHS UG1 CA233331NCI NIH HHS UG1 CA233338
6 · The paper itself

Abstract

backgroundOlder patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies. During the conception of the Beat AML design, a historical dataset was needed to help in the design of the genomic algorithm for patient assignment and serve as the basis for the statistical design of individual genomic treatment substudies for the Beat AML study.

methodsWe classified 563 newly diagnosed older AML patients treated with standard intensive chemotherapy on trials conducted by Cancer and Leukemia Group B based on the same genomic algorithm and assessed clinical outcomes.

resultsOur classification identified core-binding factor and NPM1-mutated/FLT3-ITD-negative groups as having the best outcomes, with 30-day early death (ED) rates of 0 and 20%, respectively, and median overall survival (OS) of > 1 year and 3-year OS rates of ≥ 20%. All other genomic groups had ED rates of 17-42%, median OS ≤ 1 year and 3-year OS rates of ≤ 15%.

conclusionsBy classifying patients through this genomic algorithm, outcomes were poor and not unexpected from a non-algorithmic, non-dominant VAF approach. The exception is 30-day ED rate typically is not available for intensive induction for individual genomic groups and therefore difficult to compare outcomes with targeted therapeutics. This Alliance data supported the use of this algorithm for patient assignment at the initiation of the Beat AML study. This outcome data was also used for statistical design for Beat AML substudies for individual genomic groups to determine goals for improvement from intensive induction and hopefully lead to more rapid approval of new therapies. Trial registration ClinicalTrials.gov Identifiers: NCT00048958 (CALGB 8461), NCT00900224 (CALGB 20202), NCT00003190 (CALGB 9720), NCT00085124 (CALGB 10201), NCT00742625 (CALGB 10502), NCT01420926 (CALGB 11002), NCT00039377 (CALGB 10801), and NCT01253070 (CALGB 11001).

Indexed as

MutationPrecision MedicineAgedAge FactorsAntineoplastic AgentsCytogeneticsFemalefms-Like Tyrosine Kinase 3GenomicsHumansLeukemia, Myeloid, AcuteMaleMiddle AgedNuclear ProteinsNucleophosminTreatment OutcomeAntineoplastic AgentsFLT3 protein, humanfms-Like Tyrosine Kinase 3NPM1 protein, humanNuclear ProteinsNucleophosminAcute myeloid leukemiaCytogeneticsMutationOutcomePrecision medicine

Identifiers

PMID34162404
PMCPMC8220739

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Registered trials

and 2 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.