Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2020
Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02337829 (A Phase II Study Using ACP-196), which is not on this map. Cited by 17 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 II Study Using ACP-196 (Acalabrutinib) in Patients With Relapsed/Refractory and Treatment-naïve Deletion 17p CLL/SLL: Pharmacodynamic Assessment of BTK Inhibition and Antitumor Response.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.Frontiers in immunology · 2021Pooled it
- A randomized, controlled single, and multiple ascending dose trial of the safety, pharmacokinetics and pharmacodynamics of SN1011 in healthy subjects.Clinical and translational science · 2023Trial
- Only time will tell: Modelling the kinetics of covalent inhibitors.British journal of pharmacology · 2026Review
- Peripheral and central nervous system toxicities of Bruton tyrosine kinase Inhibitors: a real-world pharmacovigilance study.Frontiers in medicine · 2026Article
- An Assessment of Kinase Selectivity, Enzyme Inhibition Kinetics and in Vitro Activity for Several Bruton Tyrosine Kinase (BTK) Inhibitors.ACS pharmacology & translational science · 2025Article
- Quantitative Systems Pharmacology Model to Predict Target Occupancy by Bruton Tyrosine Kinase Inhibitors in Patients With B-Cell Malignancies.CPT: pharmacometrics & systems pharmacology · 2025Article
- Evaluation of Bruton's Tyrosine Kinase (BTK) inhibition with alternative doses of ibrutinib in subjects with Chronic Lymphocytic Leukemia (CLL).Cancer chemotherapy and pharmacology · 2025Article
- BTK inhibition in primary central nervous system lymphoma: mechanisms, clinical efficacy, and future perspectives.Frontiers in oncology · 2024Review
- CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Assessment of ibrutinib scheduling on leukocyte, lymph node size and blood pressure dynamics in chronic lymphocytic leukemia through pharmacokinetic-pharmacodynamic models.CPT: pharmacometrics & systems pharmacology · 2023Article
- Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor.Blood · 2023Article
- Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.Clinical pharmacology in drug development · 2022Article
- Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives.Journal of clinical medicine · 2022Review
- The Role of Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions.Cancers · 2022Review
- Exploration of the prognostic signature reflecting tumor microenvironment of lung adenocarcinoma based on immunologically relevant genes.Bioengineered · 2021Article
- Discovery of a Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase with Oral Anti-Inflammatory Activity.ACS medicinal chemistry letters · 2021Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo determine the pharmacodynamic relationship between target occupancy of Bruton tyrosine kinase (BTK) and inhibition of downstream signaling. PATIENTS AND
methodsPatients with chronic lymphocytic leukemia (CLL) enrolled in a phase II clinical trial (NCT02337829) with the covalent, selective BTK inhibitor acalabrutinib donated blood samples for pharmacodynamic analyses. Study design included randomization to acalabrutinib 100 mg twice daily or 200 mg once daily and dose interruptions on day 4 and 5 of the first week. BTK occupancy and readouts of intracellular signaling were assessed sequentially between 4 and 48 hours from last dose.
resultsFour hours from last dose, BTK occupancy exceeded 96% and at trough, was higher with twice daily, median 95.3%, than with once daily dosing, median 87.6% (
conclusionsHigher BTK occupancy was achieved with twice daily over once daily dosing, resulting in deeper and more sustained inhibition of BCR signaling.
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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.