Evidence map›Paper›PMID 28402581›Full record

Trial reportAmerican journal of hematology2017

Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: Results from the N1087 alliance study.

Jeremy T Larsen, Tait D Shanafelt, Jose F Leis, Betsy LaPlant, Tim Call, Adam Pettinger, Curtis Hanson, Charles Erlichman, Thomas Matthew Habermann, Craig Reeder and 10 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in American journal of hematology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 16% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 27 citations in OpenAlex.

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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 at 4 institutions in 1 country.

Jeremy T LarsenDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Tait D ShanafeltDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Jose F LeisDivision of Hematology and Oncology, Mayo Clinic, Scottsdale, Arizona.
Betsy LaPlantAlliance Statistics, Rochester, Minnesota.
Tim CallDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Adam PettingerAlliance Statistics, Rochester, Minnesota.
Curtis HansonDivision of Hematopathology, Mayo Clinic, Rochester, Minnesota.
Charles ErlichmanDivision of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Thomas Matthew HabermannDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Craig ReederDivision of Hematology and Oncology, Mayo Clinic, Scottsdale, Arizona.
Daniel NikcevichEssentia Health-Duluth, Minnesota.
Deborah BowenDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Michael ConteDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Justin BoysenDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Charla SecretoDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Connie LesnickDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Renee TschumperDivision of Immunology, Mayo Clinic, Rochester, Minnesota.
Diane JelinekDivision of Immunology, Mayo Clinic, Rochester, Minnesota.
Neil E KayDivision of Hematology, Mayo Clinic, Rochester, Minnesota.
Wei DingDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID http://orcid.org/0000-0001-9811-4601
Mayo Clinic · USMayo Clinic in Arizona · USUniversity of Minnesota Rochester · USEssentia Health · US

Funding

TRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0M
CANCER &LEUKEMIA GROUP B STATISTICAL CENTERU10CA033601 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SARGENT, DANIEL J. · 1985 to 2013
$69.4M
Combination Therapy in B-Chronic Lymphocytic LeukemiaR01CA095241 · NCI · MAYO CLINIC ROCHESTER · PI KAY, NEIL E · 2002 to 2012
$5.7M
Targeting Oncostatin M-Receptor to Suppress Metastasis and Therapy FailureR01CA252224 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI JACKSON, MARK W. · 2021 to 2025
$2.0M
Targeting Akt Activation in CLLK23CA160345 · NCI · MAYO CLINIC ROCHESTER · PI DING, WEI · 2011 to 2015
$837k
NCI NIH HHS K23 CA160345NCI NIH HHS R01 CA095241NCI NIH HHS R01 CA252224NCI NIH HHS U10 CA025224NCI NIH HHS U10 CA033601
6 · The paper itself

Abstract

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK-2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK-2206 in combination with BR in relapsed CLL. Single-agent MK-2206 (weekly dosed) was administered one-week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2-6. Phase II employed the MTD of MK-2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6-cycle of therapy. The maximum tolerated dose of MK-2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.

Indexed as

Drug Resistance, NeoplasmAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBendamustine HydrochlorideFemaleFollow-Up StudiesHeterocyclic Compounds, 3-RingHumansLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedNeoplasm StagingRecurrenceRetreatmentRituximabBendamustine HydrochlorideHeterocyclic Compounds, 3-RingMK 2206Rituximab

Identifiers

PMID28402581
PMCPMC5507724
OpenAlexW2606699801

What OpenQuestion holds

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Registered trials

None linked

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.