Trial reportLeukemia research2017
Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia.
Trial report in Leukemia research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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
29 citing papers in PubMed, 51 citations in OpenAlex.
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Integrated computational-experimental pipeline for CHK1 inhibitor discovery: structure-based identification of novel chemotypes with anticancer activity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Advancing cancer therapy: new frontiers in targeting DNA damage response.Frontiers in pharmacology · 2024Review
- Chemical biology approaches to uncovering nuclear ROS control.Current opinion in chemical biology · 2023Review
- The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways.Cell communication and signaling : CCS · 2023Review
- Article
- Combination Therapies with Kinase Inhibitors for Acute Myeloid Leukemia Treatment.Hematology reports · 2023Review
- Targeting the DNA damage response for cancer therapy.Biochemical Society transactions · 2023Article
- Evolving DNA repair synthetic lethality targets in cancer.Bioscience reports · 2022Article
- HMGA2 expression defines a subset of human AML with immature transcriptional signature and vulnerability to G2/M inhibition.Blood advances · 2022Article
- Targeting Replication Stress Response Pathways to Enhance Genotoxic Chemo- and Radiotherapy.Molecules (Basel, Switzerland) · 2022Review
- Article
- Targeting cell cycle regulation via the G2-M checkpoint for synthetic lethality in melanoma.Cell cycle (Georgetown, Tex.) · 2021Review
- Inhibition of checkpoint kinase 1 potentiates anticancer activity of gemcitabine in bladder cancer cells.Scientific reports · 2021Article
- Review
- The POLD1Scientific reports · 2020Article
- A Genome-Wide Pooled shRNA Screen Identifies PPP2R2A as a Predictive Biomarker for the Response to ATR and CHK1 Inhibitors.Cancer research · 2020Article
- Targeting DNA Damage Response as a Strategy to Treat HPV Infections.International journal of molecular sciences · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
purposeCytosine arabinoside (AraC) remains the backbone of most treatment regimens for acute myeloid leukemia (AML). Incorporation of AraC into DNA activates checkpoint kinase 1 (Chk1), leading to cell-cycle arrest and diminished AraC cytotoxicity, which can be reversed by the selective Chk1 inhibitor MK-8776. Building on a Phase I trial, we conducted a phase II trial comparing timed sequential AraC with or without MK-8776.
methodsPatients with relapsed or primary refractory AML were randomized 1:1 to receive either AraC with MK-8776 (Arm A); or AraC alone (Arm B).
results32 patients were treated: 14 assigned to Arm A and 18 to Arm B. There were 5 (36%) complete responses (CR/CRi) and 1 (7%) partial response (PR) in Arm A, and 8 (44%) CR/CRis and 1 (6%) PR in Arm B. Median survival did not differ significantly between the two groups (5.9months in Arm A vs. 4.5 months in Arm B). MK-8776 led to a robust increase in DNA damage in circulating leukemic blasts as measured by increased γ-H2AX (16.9%±6.1% prior and 36.4%±6.8% at one hour after MK-8776 infusion, p=0.016).
conclusionResponse rates and survival were similar between the two groups in spite of evidence that MK-8776 augmented DNA damage in circulating leukemic blasts. Better than expected results in the control arm using timed sequential AraC and truncated patient enrollment may have limited the ability to detect clinical benefit from the combination.
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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.