A Study of AZD6738 and Acalabrutinib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Acerta Pharma

Status and phase: Active, not recruiting; Phase 1

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Ceralasertib; Drug: Acalabrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03328273

ACE-CL-110

2016-003737-15 (EudraCT Number)

Details and patient eligibility

About

This study evaluates the safety, pharmacokinetics, pharmacodynamics and efficacy of acalabrutinib and ceralasertib (known as AZD6738) when taken in combination.

Full description

This study is to determine the safety of ceralasertib when given as monotherapy (discontinued) and in combination with acalabrutinib in subjects with R/R CLL and in subjects who have few therapeutic options available to them. As such, this study includes a formal DLT assessment of the first 6-12 subjects dosed in Part 1 of the study. In addition, routine and regular safety monitoring will be undertaken during this study to fully assess safety of ceralasertib given as monotherapy and in combination with acalabrutinib, with toxicity assessment and dose reduction guidelines.

Enrollment: 11 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

Arm A Part 1 and 2

Other group

Description:

DISCONTINUED (ceralasertib monotherapy)

Treatment:

Drug: Ceralasertib

Arm B Part 1 and 2

Experimental group

Description:

ceralasertib + acalabrutinib in combination

Treatment:

Drug: Acalabrutinib

Drug: Ceralasertib