Chronic lymphocytic leukemia MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Calquence
Product Name: Acalabrutinib
Product Code: ACP-196
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Acalabrutinib
CAS Number: 1420477-60-6
Current Sponsor code: ACP-196
Oth
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place). 2. Diagnosis of CLL that meets all published diagnostic criteria as stated below: a. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing =1 B-cell marker (CD19, CD20, and CD23) and CD5 during screening b. Prolymphocytes may comprise 50% over a 2-month period or a lymphocyte doubling time (LDT) of 6 on the Cumulative Illness Rating Scale (CIRS) ii. Creatinine clearance of 30 to 69 ml/min using the Cockcroft-Gault equation b. Have previously received therapy for CLL and have either refractory or relapsed CLL c. Have received prior ibrutinib therapy (ie, defined as a subject who discontinued ibrutinib for any reason prior to disease progression) for CLL (please refer to protocol for definition of ibrutinib intolerance) 5. ECOG performance status of =2. 6. Female subjects of childbearing potential (ie, not surgically sterile or post-menopausal) who are sexually active with a non-sterilized male partner must use =1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 2 days after the last dose of study treatment. Contraception measures and restrictions on sperm donation are not required for male subjects. 7. Fluorescence in situ hybridization (FISH) for which the next- generation sequencing (NGS) method is preferred) within 60 days during screening up to before the first dose reflecting the presence or absence of del(17p), 13q del, 11q del, and trisomy of chromosome 12 along with the percentage of cells with the deletion, along with TP53 sequencing. Subjects must also have molecular analysis to detect IGHV mutation status (NGS is the preferred method) at screening if not done any tim
Exclusion criteria
Exclusion criteria: 1. Subjects who have had disease progression while on a BTKi for any malignant or non-malignant condition. 2. Prior malignancy (other than CLL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, early-stage prostate cancer, or other cancer from which the subject has been disease-free for =2 years. 3. History of confirmed progressive multifocal leukoencephalopathy. 4. Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months before screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval using Fridericia's formula (QTcF) >480 msec at screening. Note: Subjects with rate-controlled, asymptomatic atrial fibrillation are allowed to enroll in the study (For prior ibrutinib therapy cohort only), except in Finland, where this is applicable to all 3 cohorts. 5. Malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass. 6. Evidence of active Richter's transformation. If Richter's transformation is suspected (ie, lactate dehydrogenase [LDH] increased, asymmetric fast lymph node growth or clinical suspicion), it should be ruled out with positron emission tomography-computed tomography (PET-CT) and/or biopsy according to guidelines. 7. Central nervous system involvement by CLL. 8. Known history of human immunodeficiency virus, serologic status reflecting active hepatitis B virus or hepatitis C virus infection, any uncontrolled active systemic infection along with subjects who are on ongoing anti-infective treatment and subjects who have received vaccination with a live attenuated vaccine within 4 weeks before the first dose of study treatment. a. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antibody (anti-HBs) negative will need to have a negative hepatitis B virus PCR result before enrollment. Those who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus PCR positive will be excluded. b. Subjects who are hepatitis C virus antibody positive will need to have a negative hepatitis C virus PCR result before enrollment. Those who are hepatitis C virus PCR positive will be excluded. 9. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (>20 mg daily of prednisone or equivalent for longer than 2 weeks). 10. History of stroke or intracranial hemorrhage within 6 months before the first dose of study treatment. 11. History of bleeding diathesis (eg, hemophilia or von Willebrand disease). 12. Presence of a GI ulcer diagnosed by endoscopy within 3 months before screening. 13. Major surgical procedure within 4 weeks before first dose of study treatment. Note: Subjects who have had major surgery must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study treatment. 14. Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of acalabrutinib monotherapy in subjects with treatment-naive or relapsed/refractory chronic lymphocytic leukemia;Secondary Objective: To evaluate the investigator-assessed overall response, duration of response, and progression-free survival in subjects receiving acalabrutinib monotherapy;;Primary end point(s): Frequency, severity and relatedness of all AEs, which will also include: - Grade =3 AEs - SAEs - AESI defined as ventricular arrhythmias - AEs that lead to discontinuation of treatment - ECIs defined as cardiac events, hepatotoxicity, hypertension, infections, interstitial lung disease/pneumonitis, hemorrhage (major hemorrhage), cytopenias (anemia, leukopenia, thrombocytopenia), second primary malignancies, and tumor lysis syndrome as defined in the protocol. ;Timepoint(s) of evaluation of this end point: The final analyses at the study end | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - OR (overall response) - DOR (duration of response) - PFS (progression-free survival);Timepoint(s) of evaluation of this end point: - Overall Response (OR) will be defined as a subject's best OR to the treatment. A subject will be considered a responder if s(he) achieves CR, CRi, or PR, according to the iwCLL 2018 criteria as assessed by the investigator. - Duration of response (DOR) will be defined as the time from the first objective response of CR, CRi, or PR to the time of documented disease progression or death due to any cause, whichever occurs first. - Progression-Free Survival (PFS) will be defined as the interval from the start of study treatment to the earlier of the first documentation of disease progression or death from any cause. | — |
Countries
Australia, Brazil, Canada, Denmark, Finland, France, Germany, Italy, Korea, Republic of, Netherlands, Norway, Russian Federation, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed