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Record W2806039308 · doi:10.1016/j.clml.2018.05.022

An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma

2018· article· en· W2806039308 on OpenAlexaff
John M. Burke, Andrei R. Shustov, James Essell, Dipti Patel‐Donnelly, Jay Yang, Robert Chen, Wei Ye, Wen Shi, Sarit Assouline, Jeff P. Sharman

Bibliographic record

VenueClinical Lymphoma Myeloma & Leukemia · 2018
Typearticle
Languageen
FieldMedicine
TopicLymphoma Diagnosis and Treatment
Canadian institutionsMcGill University
FundersNational Cancer InstituteGilead Sciences
KeywordsMedicineInternal medicineGastroenterologyPeripheral edemaAnemiaHypoalbuminemiaAdverse effectLeukopeniaHyponatremiaSurgeryChemotherapy

Abstract

fetched live from OpenAlex

BACKGROUND: Entospletinib (GS-9973) is an oral, selective inhibitor of spleen tyrosine kinase. Entospletinib monotherapy was evaluated in a multicenter, phase II study of subjects with relapsed or refractory B-cell malignancy. PATIENTS AND METHODS: The study included 43 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The participants received 800 mg of the original, monomesylate formulation of entospletinib twice daily as a starting dose; the doses could be reduced because of toxicity throughout the study. RESULTS: No patient achieved a complete or partial response, 5 patients (12%) had stable disease, and 26 patients (60%) had progressive disease. Progression-free survival (PFS) at 16 weeks was 3.6% (95% confidence interval [CI], 0.3%-15.3%), and the median PFS was 1.5 months (95% CI, 1-1.7 months). The independent review committee-assessed nodal response for 27 evaluable patients showed a reduced tumor burden in 6 patients (22%). The median duration of entospletinib treatment for these 6 patients was 9 weeks (range, 3-24 weeks). One patient (4%) had a decrease of ≥ 50% in the sum of the product of the nodal diameters. The treatment-emergent adverse events occurring in ≥ 20% of the cohort were fatigue, nausea, decreased appetite, constipation, dyspnea, diarrhea, dehydration, cough, insomnia, and peripheral edema. The common laboratory abnormalities occurring in ≥ 20% of the subjects were lymphocytopenia, anemia, creatinine (chronic kidney disease), increased aspartate aminotransferase, hypoalbuminemia, total bilirubin, hyponatremia, leukopenia, increased alanine aminotransferase, increased alkaline phosphatase, and hyperglycemia. CONCLUSION: Entospletinib monotherapy at 800 mg twice daily demonstrated limited activity in patients with advanced, relapsed DLBCL.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.530
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0010.001
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.046
GPT teacher head0.384
Teacher spread0.338 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations42
Published2018
Admission routes1
Has abstractyes

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