Ceralasertib: An ATP competitive, orally bioavailable inhibitor of the Serine/Threonine protein kinase Ataxia Telangiectasia and Rad3 related (ATR).
Acalabrutinib: An experimental anti-cancer drug and Bruton's tyrosine kinase (BTK) inhibitor.
Study summary
This study evaluates the safety, pharmacokinetics, pharmacodynamics and efficacy of acalabrutinib and ceralasertib (known as AZD6738) when taken in combination.
Eligibility
Sex
ALL
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria:
* Diagnosis of relapsed or refractory CLL that meets published diagnostic criteria (International Workshop on Chronic Lymphocytic Leukemia \[IWCLL\] Hallek 2008) and supported/documented by medical records
* Subjects must be Relapse/Refractory high risk CLL and have exhausted other therapeutic options according to local/regional standard of care
* Must have received ≥1 prior therapy for treatment of their disease.
Exclusion Criteria:
* A diagnosis of ataxia telangiectasia
* Any prior exposure to an ATR inhibitor or known hypersensitivity to an excipient of the product.
* Known history of infection with human immunodeficiency virus (HIV).
* A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196 (acalabrutinib) and/or Ceralasertib
* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) \> 480 msec.
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
* Requirement of treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
* Breast feeding or pregnant
Primary outcome measure(s)
Number of participants experiencing dose-limiting toxicities — 28 Days Arm A (discontinued): When given as monotherapy in subjects with R/R high-risk CLL who have exhausted other therapeutic options according to local/regional standard of care.
Arm B: Ceralasertib given in combination with acalabrutinib in subjects with R/R high-risk CLL who are suitable for treatment with a BTK inhibitor and ceralasertib, per investigator's clinical opinion.
Trial sites (11)
Facility
City
Region
Status
Research Site
Krakow
Poland
Research Site
Lodz
Poland
Research Site
Birmingham
United Kingdom
Research Site
Bournemouth
United Kingdom
Research Site
Cardiff
United Kingdom
Research Site
Leeds
United Kingdom
Research Site
London
United Kingdom
Research Site
London
United Kingdom
Research Site
Nottingham
United Kingdom
Research Site
Oxford
United Kingdom
Research Site
Southampton
United Kingdom
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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