Actively Recruiting
A Phase 3 Trial Comparing Acalabrutinib, Obinutuzumab, and Venetoclax Versus Obinutuzumab and Venetoclax in Previously Untreated High-Risk Chronic Lymphocytic Leukemia
Led by German CLL Study Group · Updated on 2025-08-17
202
Participants Needed
30
Research Sites
N/A
Total Duration
On this page
Sponsors
G
German CLL Study Group
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating treatments for patients with high-risk chronic lymphocytic leukemia (CLL), a type of blood cancer that is aggressive and currently incurable. This phase 3, open-label, multicenter, randomized study aims to compare the effectiveness of a triple drug combination (acalabrutinib, obinutuzumab, and venetoclax) against a double combination (obinutuzumab and venetoclax) in prolonging progression-free survival (PFS) for patients with specific high-risk genetic features such as 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status. The study addresses a crucial medical need for better treatments in this difficult-to-treat group. Participants will be randomly assigned to one of two treatment groups. One group receives the triple combination of acalabrutinib, obinutuzumab, and venetoclax, while the other group receives obinutuzumab plus venetoclax. Obinutuzumab is given as intravenous infusions on specific days across six cycles. Venetoclax is taken orally with a carefully planned dose escalation and maintenance over 12 cycles. Acalabrutinib is administered orally twice daily during cycles 15 to 24. The study explores whether adding acalabrutinib improves outcomes by using these fixed-duration, chemotherapy-free regimens. Throughout the study, participants will undergo regular assessments to monitor response and safety, including checks for minimal residual disease (MRD) and overall survival. These evaluations occur up to 50 months after the first patient is enrolled. Researchers will also track progression-free survival, complete and overall response rates, event-free survival, duration of response, and time to next treatment. Safety monitoring and laboratory tests will be performed as part of study visits. The total study participation is expected to last several years to capture long-term outcomes for this high-risk patient population.
CONDITIONS
Brief Title
A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Documented diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) requiring treatment according to iwCLL criteria
- Age 18 years or older
- Presence of at least one high-risk factor: 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status
- Life expectancy of at least six months
- Platelet count greater than 30 x 10^9/l indicating adequate bone marrow function
- Creatinine clearance of 30 ml/min or higher
- Adequate liver function with total bilirubin no more than 2 times and AST/ALT no more than 2.5 times the institutional upper limit, unless related to CLL or Gilbert's Syndrome
- Negative testing for hepatitis B and hepatitis C as specified
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
You will not qualify if you...
- Previous CLL-specific treatments, except corticosteroids up to 20 mg prednisolone equivalent within 10 days before study start
- Absence of high-risk disease (no 17p-deletion, TP53 mutation, or complex karyotype)
- Severe organ or system impairment (score of 4 by CIRS), including advanced cardiac disease (NYHA class 3 or 4) limiting treatment ability
- Any life-threatening illness or condition that could affect safety or drug absorption, such as inability to swallow or gastrointestinal issues
- Transformation of CLL to Richter syndrome
- Other malignancies currently needing systemic therapy
- Active or uncontrolled infections including HIV or PML
- Use of anticoagulant therapy with warfarin or phenoprocoumon
- Pregnant or nursing women
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 24 cycles (months)
Participants receive study treatment with either the combination of acalabrutinib, obinutuzumab, and venetoclax or obinutuzumab and venetoclax alone. Treatment involves multiple cycles including intravenous infusions and oral medications over several months.
Multiple visits for infusions and monitoring throughout treatment cycles
Duration - Up to 50 months after first participant in
Participants are monitored for disease progression, treatment response, and safety after completing treatment.
Periodic visits for long-term monitoring
Trial Site Locations
Total: 30 locations
1
Helios Klinikum Bad Saarow
Bad Saarow, Germany, 15526
Actively Recruiting
2
DRK Kliniken Berlin Köpenick
Berlin, Germany, 12559
Actively Recruiting
3
Ev. Diakoniekrankenhaus
Bremen, Germany, 28239
Actively Recruiting
4
Universitätsklinik Köln
Cologne, Germany, 50937
Actively Recruiting
5
St. Johannes Hospital
Dortmund, Germany, 44137
Actively Recruiting
6
Marien Hospital Düsseldorf
Düsseldorf, Germany, 40479
Actively Recruiting
7
St. Antonius-Hospital
Eschweiler, Germany, 52249
Actively Recruiting
8
Universitaetsklinikum Essen
Essen, Germany, 45147
Actively Recruiting
9
Katholisches Krankenhaus Hagen - St. Josefs Hospital
Hagen, Germany, 58097
Actively Recruiting
10
Universitaetskliniken des Saarlandes
Homburg, Germany, 66424
Actively Recruiting
11
Klinikum Idar-Oberstein SHG
Idar-Oberstein, Germany, 55743
Actively Recruiting
12
Staedtisches Klinikum Karlsruhe
Karlsruhe, Germany, 76133
Actively Recruiting
13
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Kiel, Germany, 24116
Actively Recruiting
14
Klinikum Landshut
Landshut, Germany, 84034
Actively Recruiting
15
Klinikum Lippe-Lemgo
Lemgo, Germany, 32657
Actively Recruiting
16
St Vincenz Krankenhaus
Limburg, Germany, 65549
Actively Recruiting
17
Universitaetsklinikum Magdeburg
Magdeburg, Germany, 39120
Actively Recruiting
18
Klinikum Hochsauerland - St. Walburga Krankenhaus
Meschede, Germany, 59872
Actively Recruiting
19
KH Kliniken Maria Hilf
Mönchengladbach, Germany, 41063
Actively Recruiting
20
Krankenhaus Muenchen-Schwabing
Munich, Germany, 80804
Actively Recruiting
21
Klinikum Rechts der Isar - Technische Universitaet Muenchen
Munich, Germany, 81675
Actively Recruiting
22
Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany, 73557
Actively Recruiting
23
Klinikum Oldenburg
Oldenburg, Germany, 26133
Actively Recruiting
24
Brüderkrankenhaus St. Josef Paderborn
Paderborn, Germany, 33098
Actively Recruiting
25
Universitätsklinik Rostock
Rostock, Germany, 18057
Actively Recruiting
26
Caritas-Klinik St. Theresia
Saarbrücken, Germany, 66113
Actively Recruiting
27
Klinikum Sindelfingen-Böbingen
Sindelfingen, Germany, 71065
Actively Recruiting
28
Marienhospital Stuttgart
Stuttgart, Germany, 70199
Actively Recruiting
29
Universitaetsklinik Tuebingen
Tübingen, Germany, 72076
Actively Recruiting
30
Universitätsklinik Ulm
Ulm, Germany, 89081
Actively Recruiting
Research Team
B
Barbara Eichhorst, MD, Prof.
A
Anna Fink, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here