A Phase-3-trial of Acalabrutinib, Obinutuzumab & Venetoclax Compared to Obinutuzumab and Venetoclax in Previously Untreated Patients With High Risk CLL

NCT05197192 | Recruiting Phase 3 DMC

• 2 other identifiers: CLL162023-506414-46-00
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 30

Brief Summary

This multicenter, prospective, open-label, randomized, superiority phase 3 study is designed to demonstrate that treatment with a triple combination of acalabrutinib, obinutuzumab and venetoclax (GAVe) prolong the progression-free survival (PFS) as compared to treatment with the combination of obinutuzumab and venetoclax (GVe) in pa-tients with high risk CLL (defined as having at least one of the follow-ing risk factors: 17p-deletion, TP53-mutation, complex karyotype or an unmutated IGHV-gene status).

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL; high risk; tp53 aberration; complex karyotype; unmutated IGHV gene status

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The study is designed to demonstrate that 14 cycles of treatment with GAVe followed by up to 10 cycles maintenance with acalabrutinib for patients with detectable MRD at cycle 14 day 14 prolong PFS as compared to 12 cycles of treatment with GVe in patients with high risk CLL (defined as hav-ing at least one of the following risk factors: 17p-deletion, TP53- mutation or complex karyotype).

  50 months after FPI

Secondary Outcomes (8)

• Minimal residual disease (MRD) levels

  50 months after FPI

• MRD in PB at cycle 27 day 1

  50 months after FPI

• Overall response rate

  50 months after FPI

• Complete response rate

  50 months after FPI

• Overall Survival (OS)

  50 months after FPI

Other Outcomes (4)

• Correlation between MRD in PB/BM and PFS/OS

  50 months after FPI

• MRD by methods other than flow cytometry (ddPCR)

  50 months after FPI

• Correlation between MRD in PB and BM

  50 months after FPI

Study Arms (2)

GAVe-Arm

EXPERIMENTAL

Acalabrutinib plus Venetoclax plus Obinutuzumab plus (GAVe)

Drug: Obinutuzumab; Drug: Venetoclax; Drug: Acalabrutinib

GVe-Arm

EXPERIMENTAL

Obinutuzumab plus Venetoclax (GVe)

Drug: Obinutuzumab; Drug: Venetoclax

Interventions

Obinutuzumab DRUG

Obinutuzumab i.v. infusion: Cycle 1 Day 1: Obinutuzumab 100 mg i.v. Cycle 1 Day 1 (or 2): Obinutuzumab 900 mg i.v. Cycle 1 Day 8: Obinutuzumab 1000 mg i.v. Cycle 1 Day 15: Obinutuzumab 1000 mg i.v. Cycles 2-6: Day 1: Obinutuzumab 1000 mg i.v.

Also known as: Gazyva, Gazyvaro

GAVe-Arm; GVe-Arm

Venetoclax DRUG

Venetoclax p.o.: Cycle 1: Days 22-28: Venetoclax 20 mg (2 x 10 mg) Cycle 2: Days 1-7: Venetoclax 50 mg (1 x 50 mg) Cycle 2:Days 8-14: Venetoclax 100 mg (1 x 100 mg) Cycle 2:Days: 15-21: Venetoclax 200 mg (2 x 100 mg) Cycle 2:Days: 22-28: Venetoclax 400 mg (4 x 100 mg) Cycles 3-12: Days 1-28: Venetoclax 400 mg (4 x 100 mg)

Also known as: Venclexta, Venclyxto

GAVe-Arm; GVe-Arm

Acalabrutinib DRUG

Cycles 15-24: Days 1-28: 100 mg acalabrutinib twice daily p.o. approx. every 12 hrs (corresponding to a total daily dose of 200 mg).

Also known as: Calquence

GAVe-Arm

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• German CLL Study Group: lead
• AstraZeneca: collaborator

Study Sites (30)

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

RECRUITING

DRK Kliniken Berlin Köpenick

Berlin, 12559, Germany

RECRUITING

Ev. Diakoniekrankenhaus

Bremen, 28239, Germany

RECRUITING

Universitätsklinik Köln

Cologne, 50937, Germany

RECRUITING

St. Johannes Hospital

Dortmund, 44137, Germany

RECRUITING

Marien Hospital Düsseldorf

Düsseldorf, 40479, Germany

RECRUITING

St. Antonius-Hospital

Eschweiler, 52249, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Katholisches Krankenhaus Hagen - St. Josefs Hospital

Hagen, 58097, Germany

RECRUITING

Universitaetskliniken des Saarlandes

Homburg, 66424, Germany

RECRUITING

Klinikum Idar-Oberstein SHG

Idar-Oberstein, 55743, Germany

RECRUITING

Staedtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, 24116, Germany

RECRUITING

Klinikum Landshut

Landshut, 84034, Germany

RECRUITING

Klinikum Lippe-Lemgo

Lemgo, 32657, Germany

RECRUITING

St Vincenz Krankenhaus

Limburg, 65549, Germany

RECRUITING

Universitaetsklinikum Magdeburg

Magdeburg, 39120, Germany

RECRUITING

Klinikum Hochsauerland - St. Walburga Krankenhaus

Meschede, 59872, Germany

RECRUITING

KH Kliniken Maria Hilf

Mönchengladbach, 41063, Germany

RECRUITING

Krankenhaus Muenchen-Schwabing

Munich, 80804, Germany

RECRUITING

Klinikum Rechts der Isar - Technische Universitaet Muenchen

Munich, 81675, Germany

RECRUITING

Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

RECRUITING

Klinikum Oldenburg

Oldenburg, 26133, Germany

RECRUITING

Brüderkrankenhaus St. Josef Paderborn

Paderborn, 33098, Germany

RECRUITING

Universitätsklinik Rostock

Rostock, 18057, Germany

RECRUITING

Caritas-Klinik St. Theresia

Saarbrücken, 66113, Germany

RECRUITING

Klinikum Sindelfingen-Böbingen

Sindelfingen, 71065, Germany

RECRUITING

Marienhospital Stuttgart

Stuttgart, 70199, Germany

RECRUITING

Universitaetsklinik Tuebingen

Tübingen, 72076, Germany

RECRUITING

Universitätsklinik Ulm

Ulm, 89081, Germany

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab; venetoclax; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Barbara Eichhorst, MD, Prof.

  Department I of Internal Medicine, University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Barbara Eichhorst, MD, Prof.

CONTACT

+4922147888220; barbara.eichhorst@uk-koeln.de

Anna Fink, MD

CONTACT

+4922147888220; anna-maria.fink@uk-koeln.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: January 19, 2022
• Study Start: April 19, 2022
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (30)