Sequential Regimen of Bendamustine-Debulking Followed by ABT-199 and GA101-Induction and -Maintenance in CLL (CLL2-BAG)

NCT02401503 | Completed Phase 2

• 2 other identifiers: CLL2-BAG2014-000580-40
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

The CLL2-BAG-trial is a prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of a debulking with Bendamustine followed by an induction with GA101 (obinutuzumab) and ABT-199 (venetoclax, GDC-0199) followed by ABT-199 and GA101-maintenance in CLL patients

Conditions

Chronic Lymphocytic Leucemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria

  84 days after start of the last cycle of induction therapy

Secondary Outcomes (2)

• Adverse Events (AEs) and adverse events of special interest (AESI)

  up to 40 months after first dose of study drug

• Rate of minimal residual disease (MRD)

  up to 40 months

Study Arms (1)

Bendamustine + GA101 + ABT-199

EXPERIMENTAL

Bendamustine: 70mg/m² i.v. GA101: 1000 mg i.v. ABT-199: 20 - 400 mg p.o. Possible Re-treatment of the included patients with GA101: 1000 mg i.v. and ABT-199: 20 - 400 mg p.o.

Drug: Bendamustine; Drug: GA101; Drug: ABT-199

Interventions

Bendamustine DRUG

Debulking: Cycles 1-2, d1 \& 2: 70mg/m² i.v.

Bendamustine + GA101 + ABT-199

GA101 DRUG

Induction: Cycle 1: d1: 100mg, d1(or 2): 900mg, d8 \& 15: 1000mg; Cycle 2-6: d1: 1000mg Maintenance: Cycles 1-8 (Duration 12 weeks): d1: 1000mg

Also known as: Obinutuzumab

Bendamustine + GA101 + ABT-199

ABT-199 DRUG

Induction: Cycle 2: d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg; Cycle 3-6: d1-28: 400mg Maintenance: Cycles 1-8 (Duration 12 weeks): d1-84: 400mg

Also known as: Venetoclax, GDC-0199

Bendamustine + GA101 + ABT-199

Eligibility Criteria

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

You may qualify if:

• documented chronic lymphocytic leukemia (CLL) requiring treatment according to International Working Group on CLL (iwCLL) criteria
• adequate renal function: a creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection
• adequate hematologic function: platelets ≥ 25.000/µl, neutrophils ≥ 1.000/µl and hemoglobin ≥8.0 g/dL, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration)
• adequate liver function: total bilirubin ≤2x, aspartate aminotransferase (AST) / alanin aminotransferase (ALT) ≤2.5x the institutional upper Limit of normal (ULN) value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
• negative serological testing for hepatitis B, negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
• age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2, ECOG 3 is only permitted if related to CLL
• life expectancy ≥ 6 months
• ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

You may not qualify if:

• transformation of CLL (i.e. Richter's transformation, prolymphocytic leukemia)
• known central nervous system (CNS) involvement
• confirmed progressive multifocal leukoencephalopathy (PML)
• malignancies other than CLL currently requiring systemic therapies
• uncontrolled infection requiring systemic treatment
• any comorbidity or organ system impairment rated with a cumulative illness rating scale (CIRS) score of 4, excluding the eyes/ears/nose/throat/larynx organ system 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)
• requirement of therapy with strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors/inducers or anticoagulant with warfarin, phenprocoumon (marcumar) or other vitamin K-antagonists
• use of investigational agents within 28 days prior to registration
• known hypersensitivity to GA101 (obinutuzumab), ABT-199 (venetoclax, GDC-0199) or any of the excipients
• pregnant women and nursing mothers
• fertile men or women of childbearing potential unless surgically sterile or ≥ 2 years after the onset of menopause, or willing to use two methods of reliable contraception including one highly effective (Pearl Index \<1) and one additional effective (barrier) method during study treatment and for 18 months after end of study treatment
• vaccination with a live vaccine ≤28 days prior to registration
• legal incapacity
• prisoners or subjects who are institutionalized by regulatory or court order
• persons who are in dependence to the sponsor or an investigator

Sponsors & Collaborators

• German CLL Study Group: lead
• Hoffmann-La Roche: collaborator
• AbbVie: collaborator

Study Sites (1)

German CLL Study Group

Cologne, 50935, Germany

Location

Related Publications (3)

• Cramer P, Tausch E, von Tresckow J, Giza A, Robrecht S, Schneider C, Furstenau M, Langerbeins P, Al-Sawaf O, Pelzer BW, Fink AM, Fischer K, Wendtner CM, Eichhorst B, Kneba M, Stilgenbauer S, Hallek M. Durable remissions following combined targeted therapy in patients with CLL harboring TP53 deletions and/or mutations. Blood. 2021 Nov 11;138(19):1805-1816. doi: 10.1182/blood.2020010484.

  PMID: 34086865 BACKGROUND

• Cramer P, von Tresckow J, Bahlo J, Robrecht S, Langerbeins P, Al-Sawaf O, Engelke A, Fink AM, Fischer K, Tausch E, Seiler T, Fischer von Weikersthal L, Hebart H, Kreuzer KA, Bottcher S, Ritgen M, Kneba M, Wendtner CM, Stilgenbauer S, Eichhorst B, Hallek M. Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018 Sep;19(9):1215-1228. doi: 10.1016/S1470-2045(18)30414-5. Epub 2018 Aug 13.

  PMID: 30115596 BACKGROUND

• Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.

  PMID: 38620092 DERIVED

Related Links

• Click here for more information about this study: CLL2-BAG (German CLL Study Group)

MeSH Terms

Interventions

Bendamustine Hydrochloride; obinutuzumab; venetoclax

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Paula Cramer, Dr. med.

  German CLL Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Initial treatment: 66 patients Re-treatment: 7 patients (of the initial cohort)

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: March 27, 2015
• Study Start: May 6, 2015
• Primary Completion: December 10, 2024
• Study Completion: December 17, 2024
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)