Combination treatment for high-risk chronic lymphocytic leukemia
A Prospective, Open-label, Multicentre, Randomized, Phase-3-trial of Acalabrutinib, Obinutuzumab and Venetoclax (GAVE) Compared to Obinutuzumab and Venetoclax (GVE) in Previously Untreated Patients With High Risk Chronic Lymphocytic Leukemia (CLL)
This study is testing if a new combination of three drugs can help people with high-risk chronic lymphocytic leukemia live longer without their cancer getting worse compared to a combination of two drugs.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 202 (estimated) |
| Ages | 18 Years to 120 Years |
| Sex | All |
| Sponsor | German CLL Study Group Academic / other |
| Drugs / interventions | obinutuzumab, acalabrutinib, rituximab, ibrutinib, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 30 sites (Bad Saarow and 29 other locations) |
| Trial ID | NCT05197192 on ClinicalTrials.gov |
What this trial studies
This multicenter, open-label, randomized phase 3 trial aims to compare the effectiveness of a triple combination therapy using acalabrutinib, obinutuzumab, and venetoclax against a dual therapy of obinutuzumab and venetoclax in patients with high-risk chronic lymphocytic leukemia (CLL). The study focuses on patients with specific genetic markers indicating high risk, such as 17p-deletion, TP53-mutation, or complex karyotype. By evaluating progression-free survival, the trial seeks to address a significant medical need for more effective treatment options in this aggressive form of leukemia.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with documented high-risk CLL requiring treatment.
Not a fit: Patients without the specified genetic risk factors for high-risk CLL may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve progression-free survival for patients with high-risk CLL.
How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating high-risk CLL, indicating potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Documented CLL/SLL requiring treatment according to iwCLL criteria * Age at least 18 years * At least one of the following risk factors: 17p-deletion, TP53-mutation, complex karyotype (defined as defined as the presence of 3 or more chromosomal aberrations in 2 or more metaphases) or an unmutated IGHV gene status. * Life expectancy ≥ six months * Adequate bone marrow function indicated by a platelet count \>30 x10\^9/l * Creatinine clearance ≥ 30ml/min * Adequate liver function as indicated by a total bilirubin ≤ 2 x, AST/ ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome * Negative testing for hepatitis B (HbsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last treatment cycle),or hepatitis C (negative testing for hepatitis C RNA within 6 wee * ks prior to registration for study screening (i.e. PCR only required when serology was positive)) * ECOG (Eastern Cooperative Oncology Group Performance Status) status 0-2 Exclusion Criteria: * Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents up to 20 mg prednisolone are permitted) * Absence of high risk disease (17p-deletion, TP53-mutation complex karyotype * An individual organ/system impairment score of 4 as assessed by the CIRS definition (e.g. advanced cardiac disease (NYHA class 3 or 4) limiting the ability to receive the study treatment or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could compromise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract) * Transformation of CLL (Richter transformation) * Malignancies other than CLL currently requiring systemic therapies * Uncontrolled or active infection of HIV/PML or any other active infection * Anticoagulant therapy with warfarin or phenoprocoumon * Pregnant women and nursing mothers
Where this trial is running
Bad Saarow and 29 other locations
- Helios Klinikum Bad Saarow — Bad Saarow, Germany (Recruiting)
- DRK Kliniken Berlin Köpenick — Berlin, Germany (Recruiting)
- Ev. Diakoniekrankenhaus — Bremen, Germany (Recruiting)
- Universitätsklinik Köln — Cologne, Germany (Recruiting)
- St. Johannes Hospital — Dortmund, Germany (Recruiting)
- Marien Hospital Düsseldorf — Düsseldorf, Germany (Recruiting)
- St. Antonius-Hospital — Eschweiler, Germany (Recruiting)
- Universitaetsklinikum Essen — Essen, Germany (Recruiting)
- Katholisches Krankenhaus Hagen - St. Josefs Hospital — Hagen, Germany (Recruiting)
- Universitaetskliniken des Saarlandes — Homburg, Germany (Recruiting)
- Klinikum Idar-Oberstein SHG — Idar-Oberstein, Germany (Recruiting)
- Staedtisches Klinikum Karlsruhe — Karlsruhe, Germany (Recruiting)
- Universitaetsklinikum Schleswig-Holstein Campus Kiel — Kiel, Germany (Recruiting)
- Klinikum Landshut — Landshut, Germany (Recruiting)
- Klinikum Lippe-Lemgo — Lemgo, Germany (Recruiting)
- St Vincenz Krankenhaus — Limburg, Germany (Recruiting)
- Universitaetsklinikum Magdeburg — Magdeburg, Germany (Recruiting)
- Klinikum Hochsauerland - St. Walburga Krankenhaus — Meschede, Germany (Recruiting)
- KH Kliniken Maria Hilf — Mönchengladbach, Germany (Recruiting)
- Krankenhaus Muenchen-Schwabing — Munich, Germany (Recruiting)
- Klinikum Rechts der Isar - Technische Universitaet Muenchen — Munich, Germany (Recruiting)
- Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd — Mutlangen, Germany (Recruiting)
- Klinikum Oldenburg — Oldenburg, Germany (Recruiting)
- Brüderkrankenhaus St. Josef Paderborn — Paderborn, Germany (Recruiting)
- Universitätsklinik Rostock — Rostock, Germany (Recruiting)
- Caritas-Klinik St. Theresia — Saarbrücken, Germany (Recruiting)
- Klinikum Sindelfingen-Böbingen — Sindelfingen, Germany (Recruiting)
- Marienhospital Stuttgart — Stuttgart, Germany (Recruiting)
- Universitaetsklinik Tuebingen — Tübingen, Germany (Recruiting)
- Universitätsklinik Ulm — Ulm, Germany (Recruiting)
Study contacts
- Principal investigator: Barbara Eichhorst, MD, Prof. — Department I of Internal Medicine, University Hospital Cologne
- Study coordinator: Barbara Eichhorst, MD, Prof.
- Email: barbara.eichhorst@uk-koeln.de
- Phone: +4922147888220
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.