Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014
Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 5 of them syntheses that pooled 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.
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.
Who cites it
120 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Antileukemic therapies for older adults with AML ineligible for conventional therapy: systematic review and meta-analysis.Blood advances · 2026Pooled it
- American Society of Hematology 2025 guidelines for treating newly diagnosed acute myeloid leukemia in older adults.Blood advances · 2026Guideline
- Efficacy of epigenetic agents for older patients with acute myeloid leukemia and myelodysplastic syndrome in randomized controlled trials: a systematic review and network meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Pooled it
- Targeting epigenetic pathways in acute myeloid leukemia and myelodysplastic syndrome: a systematic review of hypomethylating agents trials.Clinical epigenetics · 2016Pooled it
- A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML.Blood neoplasia · 2025Trial
- Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome.Annals of hematology · 2025Trial
- Reduced dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia following intensive or low-intensity induction: a single-centre, single-arm, phase 2 trial.The Lancet. Haematology · 2024Trial
- Guadecitabine vs treatment choice in newly diagnosed acute myeloid leukemia: a global phase 3 randomized study.Blood advances · 2023Trial
- Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS.Blood advances · 2020Trial
- Trial
- Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study.Blood advances · 2019Trial
- Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia.Blood advances · 2018Trial
- Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.Leukemia · 2016Trial
- Azacitidine with or without Entinostat for the treatment of therapy-related myeloid neoplasm: further results of the E1905 North American Leukemia Intergroup study.British journal of haematology · 2016Trial
- A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia.Investigational new drugs · 2015Trial
- Trial
- Sequential azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia: a single-arm, phase 1/2 study.The Lancet. Haematology · 2015Trial
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
purposeAlthough azacitidine (AZA) improves survival in patients with high-risk myelodysplastic syndrome, the overall response remains approximately 50%. Entinostat is a histone deacetylase inhibitor that has been combined with AZA with significant clinical activity in a previous phase I dose finding study.
designOpen label phase II randomized trial comparing AZA 50 mg/m(2)/d given for 10 days ± entinostat 4 mg/m(2)/d day 3 and day 10. All subtypes of myelodysplasia, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes were eligible for the study. The primary objective was the rate of hematologic normalization (HN; complete remission + partial remission + trilineage hematological improvement).
resultsOne hundred forty-nine patients were analyzed, including 97 patients with myelodysplastic syndrome and 52 patients with acute myeloid leukemia. In the AZA group, 32% (95% CI, 22% to 44%) experienced HN and 27% (95% CI, 17% to 39%) in the AZA + entinostat group. Both arms exceeded the HN rate of historical control (Cancer and Leukemia Group B 9221 trial), but only the AZA group fulfilled the primary objective of the study. Rates of overall hematologic response were 46% and 44%, respectively. Median overall survivals were 18 months for the AZA group and 13 months for the AZA + entinostat group. The combination arm led to less demethylation compared with the monotherapy arm, suggesting pharmacodynamic antagonism.
conclusionAddition of entinostat to AZA did not increase clinical response as defined by the protocol and was associated with pharmacodynamic antagonism. However, the prolonged administration of AZA by itself seems to increase HN rate compared with standard dosing and warrants additional investigation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.