AVO-CLL: a phase III multicenter, randomized, open-label, clinical trial comparing efficacy and safety of acalabrutinib in combination with obinutuzumab versus venetoclax in combination with obinutuzumab in the first-line treatment of newly diagnosed patients with chronic lymphocytic leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Jul 2024 → ongoing

Decision date (initial)

2024-04-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Main objective of the study: to evaluate the therapeutic efficacy, safety and tolerability of acalabrutinib in combination with obinutuzumab versus venetoclax in combination with obinutuzumab in the treatment of patients with chronic lymphocytic leukemia.

Secondary objectives 1

1. Additional aim of the study: to assess the quality of life of study participants using the EORTC QLQ-c30, EQ-5D, FACIT-Fatigue questionnaires and to compare the results of the group of participants treated with acalabrutinib in combination with obinutuzumab (group A) with the group of participants treated with venetoclax combined with obinutuzumab (group B). ). ​

Conditions and MedDRA coding

Chronic lymphocytic leukemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Written informed consent to participate in a clinical trial 2. Age of patients over 18 years (women and men) 3. Diagnosis of chronic lymphocytic leukemia untreated before the screening visit 4. Presence of the following parameters during the screening period: - presence of monoclonal lymphocytes with co-expression of B cell markers (CD19, CD20 and CD23) and CD5 - prolymphocyte count <55% of peripheral blood lymphocyte count - absolute number of peripheral blood lymphocytes > 5000 /ul 5. Presence of indications to start treatment according to the International Workshop on Chronic Lymphocytic Leukemia (the National Cancer Institute-Working Group (IWCLL) 2018. 6. Laboratory test results: - absolute ANC number ≥0.75 x 109 /l or ≥0.50x109 /l in patients with documented bone marrow involvement; - platelet count ≥50x10 /l or ≥30x109 /l in patients with documented bone marrow involvement; - total bilirubin ≤1.5xULN; - AST, ALT, GGT in serum ≤3.0xULN; - estimated creatinine clearance (eGFR) ≥30 ml/min; - negative test result for HBsAg and HBcAg 7. ECOG performance assessment score ≤2. 8. Use of effective contraception by women of childbearing potential during treatment and at least 2 days after the last dose of acalabrutinib, 30 days after the last dose of venetoclax and 18 months after the last dose of obinutuzumab 9. Use of an effective form of contraception by men during the study and 90 days after taking the last dose of the IMP 10. Men must refrain from donating sperm during the study and for 90 days after taking the last dose of the study drug

Exclusion criteria 1

1. 1. Any previous systemic treatment for CLL 2. Diagnosis of CNS lymphoma or leukemia 3. Diagnosed prolymphocytic leukemia or previous or suspected Richter's syndrome; 4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purple 5. Major surgery within 4 weeks before the first dose of IMP 6. Previous malignancy, except appropriately treated melanoma arising from malignant lentigo, non-melanoma skin cancer, cervical cancer “in situ”, or other treated malignancy without evidence of active disease >3 years prior to screening and at low risk of recurrence 7. Serious cardiovascular disease, e.g., uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months before study entry, or any New York Heart Association Functional Classification class 3 or 4 heart disease or QTc >480 msec before entering the study 8. Previous stroke or intracranial hemorrhage within 6 months before randomization; 9. Current or planned anticoagulant treatment with warfarin or vitamin K antagonists within 7 days of the first dose of the study drug 10. Current or planned treatment with proton pump inhibitors 11. Current or planned treatment with a strong CYP3A inhibitor/inducer 12. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before the screening visit 13. history of HIV infection 14. History of bleeding disorders 15. The presence of contraindications to use of IMP according to Summary of Product Characteristics 16. Lack of full legal capacity 17. Lack of possibility to understand the purpose

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint Progression-free survival (PFS), defined as the time from randomization to progression or death, a clinically important endpoint.

Secondary endpoints 1

1. Secondary endpoints Response to treatment (including MRD), time to next line of treatment. The amount of change in quality of life. Treatment safety based on the assessment of adverse events. Overall survival is defined as the time from randomization to death from any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Sponsor organisation

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Address

Ul. Alfreda Sokolowskiego 4

City

Walbrzych

Postcode

58-309

Country

Poland

Scientific contact point

Organisation

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Contact name

prof. Aleksandra Butrym

Public contact point

Organisation

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego

Contact name

prof. Aleksandra Butrym

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications