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Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase

2020· article· en· W3093975417 on OpenAlexfundno aff
John Mascarenhas, Raajit K. Rampal, Heidi Kosiorek, Rupali Bhave, Elizabeth O. Hexner, Eunice S. Wang, Aaron T. Gerds, Camille N. Abboud, Marina Kremyanskaya, Dimitry Berenzon, Olatoyosi Odenike, Noushin Farnoud, Aishwarya Krishnan, Rona Singer Weinberg, Erin McGovern, Mohamed E. Salama, Vesna Najfeld, Juan S. Medina-Martínez, Juan Arango Ossa, Max F. Levine, Yangyu Zhou, Lonette Sandy, Mark Heaney, Ross L. Levine, Ruben A. Mesa, Amylou C. Dueck, Ronald Hoffman

Bibliographic record

VenueBlood Advances · 2020
Typearticle
Languageen
FieldMedicine
TopicMyeloproliferative Neoplasms: Diagnosis and Treatment
Canadian institutionsnot available
FundersNational Cancer InstituteGenentechNational Institutes of HealthAstellas PharmaMacroGenicsGalectoSierra OncologyCTI BiopharmaIncyteMemorial Sloan-Kettering Cancer CenterGilead SciencesCardinal HealthAmgenPfizerPTC TherapeuticsCelgeneEli Lilly and CompanyAstraZenecaAgios Pharmaceuticals
KeywordsRuxolitinibDecitabineMedicineMyeloproliferative neoplasmInternal medicinePhases of clinical researchConfidence intervalPopulationClinical endpointOncologyGastroenterologyClinical trialMyelofibrosisSurgeryBone marrow

Abstract

fetched live from OpenAlex

Myeloproliferative neoplasms (MPN) that have evolved into accelerated or blast phase disease (MPN-AP/BP) have poor outcomes with limited treatment options and therefore represent an urgent unmet need. We have previously demonstrated in a multicenter, phase 1 trial conducted through the Myeloproliferative Neoplasms Research Consortium that the combination of ruxolitinib and decitabine is safe and tolerable and is associated with a favorable overall survival (OS). In this phase 2 trial, 25 patients with MPN-AP/BP were treated at the recommended phase 2 dose of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle. Nineteen patients died during the study follow-up. The median OS for all patients on study was 9.5 months (95% confidence interval, 4.3-12.0). Overall response rate (complete remission + incomplete platelet recovery + partial remission) was 11/25 (44%) and response was not associated with improved survival. We conclude that the combination of decitabine and ruxolitinib was well tolerated, demonstrated favorable OS, and represents a therapeutic option for this high-risk patient population. This trial was registered at www.clinicaltrials.gov as #NCT02076191.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.001

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 head0.019
GPT teacher head0.302
Teacher spread0.282 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized 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

Citations72
Published2020
Admission routes1
Has abstractyes

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