acalabrutinib for Chronic lymphocytic leukaemia (CLL) | Small lymphocytic lymphoma (SLL)

Inclusion criteria

• {"criterion_text":"- 1. Participant must be ≥ 18 years at the time of signing informed consent.\n- 2. Diagnosis of CLL/SLL according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines 2018 (Hallek et al. 2018)\n- 3. Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ partial remission (PR) (i.e., complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or PR) with a minimum of 2 years since the end of the prior 1L treatment.\n- 4. The following data must be available or at least the appropriate samples drawn/acquired prior to dosing: a) variable region of immunoglobulin heavy chain (IGHV) (mutated vs. unmutated) b) 17p deletion [del(17p)] (present or absent) c) Tumor protein 53 (TP53) mutation (present or absent)\n- 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2\n- 6. Adequate organ and bone marrow (BM) function."}

Exclusion criteria

• {"criterion_text":"- 1. Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.\n- 10. History of hypersensitivity or anaphylaxis to study intervention(s).\n- 11. Requires treatment with a strong CYP3A4 inhibitor/inducer.\n- 12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.\n- 13. Major surgical procedure within 30 days of the first dose of study intervention.\n- 2. Significant cardiovascular or cerebrovascular disease.\n- 3. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).\n- 4. Child-Pugh B/C liver cirrhosis.\n- 5. History of prior or current malignancy.\n- 6. HIV positive\n- 7. History of progressive multifocal leukoencephalopathy (PML).\n- 8. Active hepatitis B or C infection:\n- 9. Corticosteroid use > 20 mg within 1 week before the first dose of study intervention."}

Primary endpoints

• {"endpoint_text":"- ORR, defined as the proportion of participants who achieve best response of complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (Hallek et al, 2018) as assessed by the investigator, with timepoint of primary interest after completion of Cycle 14.","definition_or_measurement_approach":"ORR measured as proportion of participants achieving best response (CR, CRi, nPR, or PR) per iwCLL criteria (Hallek et al, 2018) assessed by the investigator; primary timepoint after completion of Cycle 14."}

Secondary endpoints

• {"endpoint_text":"- 1) Efficacy: PFS, defined as time from date of the first dose until progression per iwCLL criteria (Hallek et al, 2018) as assessed by the investigator, or death due to any cause in the absence of progression. The measure of interest is the median of PFS.","definition_or_measurement_approach":"PFS: time from first dose until progression per iwCLL criteria (investigator-assessed) or death; measure of interest = median PFS."}
• {"endpoint_text":"- 2) Efficacy: DoR, defined as the time from the date of first documented response until date of documented progression per iwCLL criteria (Hallek et al, 2018) as assessed by the investigator, or death due to any cause. The measure of interest is the median of DoR.","definition_or_measurement_approach":"DoR: time from first documented response to documented progression per iwCLL (investigator-assessed) or death; measure = median DoR."}
• {"endpoint_text":"- 3) Efficacy: EFS, defined as the time from date of the first dose until the first occurrence of disease progression, initiation of subsequent CLL/SLL therapy, or death due to any cause. The measure of interest is the median of EFS.","definition_or_measurement_approach":"EFS: time from first dose until first of disease progression, start of subsequent CLL/SLL therapy, or death; measure = median EFS."}
• {"endpoint_text":"- 4) Efficacy: TTNT, defined as the time from date of the first dose to the initiation of subsequent CLL/SLL therapy or death due to any cause. The measure of interest is the median of TTNT","definition_or_measurement_approach":"TTNT: time from first dose to initiation of subsequent CLL/SLL therapy or death; measure = median TTNT."}
• {"endpoint_text":"- 5) Efficacy: OS, defined as the time from date of the first dose until the date of death due to any cause. The timepoint of interest is the landmark estimate of OS at 5 years.","definition_or_measurement_approach":"OS: time from first dose until death from any cause; timepoint of interest = landmark estimate at 5 years."}
• {"endpoint_text":"- 6) Efficacy: Rate of peripheral blood (PB) uMRD, defined as proportion of participants achieving remission based on a clonoSEQ® assay result of < 1 CLL cell per 100,000 leukocytes (< 10^-5). The timepoint of interest is the rate of uMRD at 3 months after last treatment dose","definition_or_measurement_approach":"PB uMRD: proportion with clonoSEQ result <1 CLL cell per 100,000 leukocytes (<10^-5); timepoint = 3 months after last treatment dose."}
• {"endpoint_text":"- 7) Safety: Safety and tolerability will be evaluated in terms of adverse event (AE)s/serious adverse event (SAE)s, AEs leading to treatment discontinuation and deaths, event(s) of clinical interest (ECI)s and relevant clinical laboratory results","definition_or_measurement_approach":"Safety/tolerability assessed by incidence of AEs/SAEs, AEs leading to discontinuation, deaths, events of clinical interest (ECIs), and relevant clinical laboratory results."}

Methods

• Site-based recruitment at participating hospitals/clinics listed per country (site names and local contacts are provided in CTIS trial sites).
• Use of recruitment brochures and recruitment process documents (K2_Brochure, K1_Recruit-ICF process) provided per country; country-specific patient-facing materials and brochures are available in multiple languages as listed in CTIS (examples: Spanish, Italian, Czech, Polish, Ukrainian, German, English).

Austria

Earliest CTIS Part Ii Submission Date

03-04-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

27

Number Of Sites

1

Number Of Participants

8

Czechia

Earliest CTIS Part Ii Submission Date

27-03-2026

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

33

Number Of Sites

3

Number Of Participants

14

Ireland

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

01-05-2026

Processing Time Days

21

Number Of Sites

2

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

27-03-2026

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

38

Number Of Sites

5

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

12-03-2026

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

46

Number Of Sites

8

Number Of Participants

11

Poland

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

20

Number Of Sites

5

Number Of Participants

13

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: 1,10,11,12,13,2,3,4,5,6,7,8

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: 1,10,11,12,13,2,3,4,5,6,7,8","organisation_type":"Pharmaceutical company"}