Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma MedDRA version: 21.1 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Calquence
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Acalabrutinib
Current Sponsor code: ACP-196
Other descriptive name: Acalabrutinib
Concentration unit: mg milligram(s)
Conc
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participant must be = 18 years at the time of screening. - 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 Minimal Residual Disease. - Adequate BM function independent of growth factor or platelet transfusion support within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL/SLL: (a) Absolute neutrophil count = 1.0 × 10^9/L. (b) Platelet counts = 30 × 10^9/L; in cases of thrombocytopenia clearly due to CLL/SLL (per the discretion of the investigator), platelet count should be = 10 × 10^9/L. - Estimated CrCL > 30 mL/min calculated according to Cockcroft-Gault (using actual body weight), or serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: - 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. - 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. - Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease). - Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. - History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study intervention. - Child-Pugh B/C liver cirrhosis. - History of prior or current malignancy (including but not limited to known CNS lymphoma/leukemia or known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome) that could affect compliance with the protocol or interpretation of results. Exceptions can be made for the following based on physician discretion: (a) Curatively treated basal cell carcinoma or squamous cell carcinoma 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 not specified above that have been curatively treated by surgery and/or radiation therapy from which the participant is disease-free for = 3 years without further treatment. - Any prior CLL/SLL-specific therapies, except prior rituximab if used for autoimmune cytopenias and not as anti-CLL/SLL treatment. - 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. - 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. - 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 shorter) prior to registration for study screening. - Prothrombin time (PT)/INR or activated partial thromboplastin time, in the absence of lupus anticoagulant, > 2 × ULN. - Currently pregnant (confirmed with positive pregnancy test) or breast feeding. - Women of Childbearing Potential (WOCBP) unless the following criteria are met - a negative pregnancy test is required for all WOCBP within 21 days before start of study intervention, followed by immediate highly effective contraception; further pregnancy testing will be performed monthly.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether MRD-driven finite AV treatment is NI to MRD-driven finite VO treatment with respect to PFS.;Secondary Objective: - To assess the effect of AV treatment compared with VO treatment on uMRD at sequential timepoints - To assess the effect of AV treatment compared with VO treatment on OS - To assess the effect of AV treatment compared with VO treatment on EFS - To assess the effect of AV treatment compared with VO treatment on ORR - To assess symptoms, functional status, global health status/QoL, and patient perceived benefitrisk in participants treated with AV versus VO using the EORTC QLQ-C30, EORTC QLQCLL17, NCI PRO-CTCAE item for Bruising, and PGI-BR;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: The primary analysis is event-based and will be conducted after enrollment is completed and approximately 112 investigator-assessed PFS events have occurred. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of peripheral blood uMRD - Overall survival - Event-free survival - Overall response rate - CR rate after completion of 12 cycles of venetoclax - Change from baseline in EORTC QLQ-C30, EORTC QLQ-CLL17 scales - Proportion of participants experiencing bruising - Proportion of participants reporting each response option of the PGI-BR;Timepoint(s) of evaluation of this end point: The initial analysis of the study will be conducted on the key secondary endpoint, uMRD rate after 6 and 12 cycles of venetoclax. The analysis will be conducted at approximately 33 and 39 months, respectively, after the first participant is randomized (assuming 24 months enrollment and 9- and 15-months treatment periods, respectively). | — |
Countries
Australia, France, Hungary, Poland, Spain, United States
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed