ACALABRUTINIB for Chronic lymphocytic leukaemia | Small lymphocytic lymphoma

Inclusion criteria

• {"criterion_text":"- Participant must be ≥ 18 years at the time of signing the consent form\n- Documented TN CLL/SLL requiring treatment according to iwCLL guidelines 2018 (Hallek et al 2018) including a detectable clonal B-cell population at baseline for purposes of measuring for MRD\n- Adequate BM function independent of growth factor or platelet transfusion support within 2 weeks of screening initiation as follows: (a) Absolute neutrophil count ≥ 1.0 × 10^9/L; absolute neutrophil count ≥ 500 cells/μL (≥ 0.50 × 10^9/L) with documented BM involvement of CLL/SLL (b) Platelet counts ≥ 30 × 10^9/L; platelet count ≥ 10 × 10^9/L in participants with documented BM involvement of CLL/SLL\n- Estimated CrCL of ≥ 30 mL/min, calculated by Cockcroft-Gault (using actual body weight), or serum creatinine < 2 × ULN: Males: CrCL (mL/min) = Weight (kg) × (140 - Age) / 72 × serum creatinine (mg/dL) Females: CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85 / 72 × serum creatinine (mg/dL)\n- Meet the following laboratory parameters (ULN is based on institutional standards): (a) Serum AST and ALT ≤ 3 × ULN (Higher thresholds may be allowed if hepatic dysfunction is attributable to CLL/SLL and after discussion with the Sponsor Hematology Safety Knowledge Group). (b) Total bilirubin ≤ 1.5 × ULN, unless directly attributable to Gilbert's syndrome\n- An ECOG performance status of 0 to 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing"}

Exclusion criteria

• {"criterion_text":"- As judged by the investigator, any evidence of past or current diseases that, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize their safety or compliance with the protocol or would put the study at risk\n- Requires treatment with a strong cytochrome CYP3A4 inhibitor/inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited\n- Concurrent participation in another therapeutic clinical trial. Use of investigational agents that interfere with the study intervention(s) within 30 days or 5 half-lives (whichever is longer) prior to registration for study screening\n- Prothrombin time/INR or activated partial thromboplastin time, in the absence of lupus anticoagulant or attributed to anticoagulant (eg, direct oral anticoagulant) > 2 × ULN\n- Currently pregnant (confirmed with positive pregnancy test) or breast feeding\n- WOCBP unless the following criteria are met: a negative pregnancy test at least 30 days before start of study intervention, followed by immediate highly effective contraception; further pregnancy testing will be performed every cycle and as clinically indicated.\n- Clinically significant cardiovascular disease, such as 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\n- Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease)\n- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura\n- History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study intervention\n- Child-Pugh B/C liver cirrhosis\n- History of prior or current malignancy (including but not limited to known central nervous system involvement such as by CLL/SLL, leptomeningeal disease, or spinal cord compression, known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome) that could affect compliance with the protocol or interpretation of results. Possible examples where compliance or data interpretation may not be affected could include the following, per physician discretion. (a) Curatively treated BCC or SCC of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study. (b) Other cancers that have been curatively treated from which the participant is disease-free for ≥ 3 years without further treatment\n- Any prior CLL/SLL-specific therapies, except prior rituximab if used for autoimmune cytopenias and not as anti-CLL/SLL treatment\n- Corticosteroid use > 20 mg within 1 week before the first dose of study intervention, except as indicated for other medical conditions, such as autoimmune cytopenias, inhaled steroid for asthma, topical steroid use, or as premedication for administration of study intervention or contrast"}

Primary endpoints

• {"endpoint_text":"- PFS, defined as the time from the date of randomization until date of objective progressive disease per iwCLL 2018 criteria as assessed by the investigator or death from any cause in the absence of progression","definition_or_measurement_approach":"Defined as the time from the date of randomization until date of objective progressive disease per iwCLL 2018 criteria as assessed by the investigator or death from any cause in the absence of progression"}

Secondary endpoints

• {"endpoint_text":"- Rate of peripheral blood uMRD","definition_or_measurement_approach":"Peripheral blood uMRD rate (no further definition provided in the CTIS entries)"}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"Overall survival (OS) as recorded (no further definition provided in the CTIS entries)"}
• {"endpoint_text":"- Event-free survival","definition_or_measurement_approach":"Event-free survival (EFS) as recorded (no further definition provided in the CTIS entries)"}
• {"endpoint_text":"- Overall response rate","definition_or_measurement_approach":"Overall response rate (ORR) as recorded (no further definition provided in the CTIS entries)"}
• {"endpoint_text":"- CR rate after completion of 12 cycles of venetoclax","definition_or_measurement_approach":"Complete response (CR) rate assessed after completion of 12 cycles of venetoclax"}
• {"endpoint_text":"- Change from baseline in EORTC QLQ-C30, EORTC QLQ-CLL17 scales","definition_or_measurement_approach":"Change from baseline measured using the EORTC QLQ-C30 and EORTC QLQ-CLL17 patient-reported outcome instruments"}
• {"endpoint_text":"- Proportion of participants experiencing bruising","definition_or_measurement_approach":"Proportion of participants reporting bruising (PRO measurement; secondary objectives reference use of NCI PRO-CTCAE item for Bruising)"}
• {"endpoint_text":"- Proportion of participants reporting each response option of the PGI-BR","definition_or_measurement_approach":"Proportion reporting each response option on the Patient Global Impression of Benefit-Risk (PGI-BR) instrument"}

Czechia

Latest Decision Or Authorization Date

26-02-2025

Number Of Sites

3

Number Of Participants

100

Spain

Latest Decision Or Authorization Date

24-02-2025

Number Of Sites

2

Number Of Participants

27

France

Latest Decision Or Authorization Date

24-02-2025

Number Of Sites

2

Number Of Participants

67

Poland

Latest Decision Or Authorization Date

24-07-2025

Number Of Sites

6

Number Of Participants

142

Hungary

Latest Decision Or Authorization Date

21-10-2025

Number Of Sites

2

Number Of Participants

51

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Parexel International Corp.

Responsibilities

Sponsor duties codes: [1,10,11,12,15 (Medical Management),2,5,6,7,8,9]; contact Clinicaltrial.Enquiries@parexel.com; phone +35314739500

Third parties

• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Sponsor duties codes present in CTIS record: [1,10,11,12,15 (Medical Management),2,5,6,7,8,9]; contact email Clinicaltrial.Enquiries@parexel.com; phone +35314739500","organisation_type":"Pharmaceutical company"}