Trial reportPloS one2015
Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies.
Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 27 papers, 1 of them a synthesis 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.
A Phase 1, Open-label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myelogenous Leukemia (AML).
Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy
A Phase 2, Monocentric, Pilot Study to Evaluate Safety and Efficacy of CC 486 (Oral Azacitidine) Plus Best Supportive Care as Maintenance of Response to sc Azacitidine in IPSS Higher Risk Elderly MDS Patients
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.The oncologist · 2018Pooled it
- Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- CC-486 Maintenance after Stem Cell Transplantation in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018Trial
- Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Trial
- Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes.Leukemia · 2016Trial
- A phase 1/1b study of the all-oral regimen CC-486 and venetoclax in acute myeloid leukemia.Blood advances · 2026Article
- Review
- Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2024Review
- Extended exposure to low doses of azacitidine induces differentiation of leukemic stem cells through activation of myeloperoxidase.Haematologica · 2024Article
- Optimal Post-Remission Consolidation Therapy in Patients with AML.Acta haematologica · 2024Review
- Evaluation of Drug Effectiveness and Controlled Release Profiles of Clay Minerals Loaded with Anti-Carcinogenic Agent as a Drug Delivery System on Leukemia.Cancer management and research · 2024Article
- Management of Patients with Lower-Risk Myelodysplastic Neoplasms (MDS).Current oncology (Toronto, Ont.) · 2023Review
- A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer.Clinical epigenetics · 2023Article
- Older Patients with Acute Myeloid Leukemia Deserve Individualized Treatment.Current oncology reports · 2022Review
- New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy.International journal of molecular sciences · 2022Review
- Article
- Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy.Frontiers in immunology · 2022Review
- Oral hypomethylating agents: beyond convenience in MDS.Hematology. American Society of Hematology. Education Program · 2021Article
- Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives.Cancers · 2021Review
- Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
unlabelledCC-486 (oral azacitidine) is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05) reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle), with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle.
trial registrationClinicalTrials.gov NCT00528983.
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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.