DCLLSG

CLL2-BAG Trial

Title A prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by GA101 (obinutuzumab) and ABT-199 (venetoclax) followed by ABT-199 and GA101 maintenance in CLL patients
Protocol IDs EudraCT: 2014-000580-40
NCT02401503
Status in extended follow up
In the event of a relapse, study patients already enrolled have the option of being re-treated with obinutuzumab and venetoclax
Contact Medical Management: Dr. Paula Cramer

Dr. Paula Cramer
+49 221 478-88220 (Office)
paula.cramer@uk-koeln.de

Project Management: Marie Kronmüller

Marie Kronmüller
+49 221 478-88157
marie.kronmueller@uk-koeln.de

Data Management: Olga Korf

Olga Korf
+49 221 478-96124
olga.korf@uk-koeln.de

Safety Management: Sabine Frohs

Sabine Frohs
+49 221 478-89621
sabine.frohs@uk-koeln.de

Contact for scientific queries Dr. Paula Cramer

Dr. Paula Cramer
+49 221 478-88220 (Office)
paula.cramer@uk-koeln.de

Dr. Anna Fink

Dr. Anna Fink
+49 221 478-88198
anna-maria.fink@uk-koeln.de

Design Prospective, multicenter, single-arm, open-label phase-II trial
Objective To evaluate the efficacy and the safety of the therapeutic regimen
Primary Endpoint Overall response rate (ORR) at final restaging (RE) including all patients
achieving CR, CRi or PR
Secondary Endpoints Safety parameters: AEs, AESI and their relationship to study treatment
Target Population - According to amendment 4 only patients already included in the CLL2-BAG trial qualify for re-treatment with venetoclax and obinutuzumab. Re-treatment is scheduled to start by the end of September 2020. No new patients will be recruited.
- B-CLL according to iwCLL criteria (2008), requiring treatment
- Previously untreated or relapsed/refractory CLL
- ECOG performance status 0 – 2 (ECOG 3 only permitted if related to CLL)
- Age  ≥ 18 years
Treatment Debulking
2 debulking cycles of bendamustine will be administered unless the patient has a contraindication or a debulking is not clinically indicated
Bendamustin i.v.
Cycle 1 - 2: 70 mg/m², d1-2
q 28d
Please note: Patients re-treated with venetoclax and obinutuzumab (amendment 4) receive no debulking with bendamustine
Induction
Obinutuzumab
i.v.
Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg
Cycle 2 - 6: 1000 mg, d1
+ Venetoclax p.o.
Cycle 2: Dose eskalation d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg
Cycle 3 - 6: 400 mg daily
q 28d
During the phase of staging between induction and maintenance the intake of Venetoclax is continued.
Maintenance
Obinutuzumab i.v.
Cycle 1 - 8: 1000 mg, d1
+ Venetoclax p.o.
Cycle 1 - 8: 400 mg daily
q 84d

Maintenance treatment will be continued until (whichever occurs first):
- 3 months after confirmation of achievement of MRD negativity in patients with a (clinical) CR/CRi,
- progression of CLL or start of a subsequent therapy
- unacceptable toxicity
- maintenance cycle 8
Patients recruited 66 patients ( re-treatment: up to 20 patients)
Time schedule Recruitment period: 06 May 2015 - 04 January 2016
Re-Screening: by the end of Q3/2020
End of study: Q3/2022
Protocol Version 12 March 2015 Protocol (Version 2.2)
21 October 2015 Amendment 1 (Version 3.0)
22 August 2016 Amendment 2 (Version 4.0)
07 June 2017 Amendment 3 (Version 5.0)
11 Nov 2019 Amendment 4 (Version 6.0)
Sponsor University of Cologne
Principal Investigator Dr. med. Paula Cramer, Department I of Internal Medicine, University Hospital of Cologne
Coordinating Physician Dr. med. Anna Fink
Documents
(publicly available)
Synopsis incl. Amendment 4 (Version 6.0 | 11 Nov 2019)
Documents
(password protected)
Protocol and other documents see Download Center
Publications 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, Böttcher 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 Aug 13 pii: S1470-2045(18)30414-5. doi: 10.1016/S1470-2045(18)30414-5. [Epub ahead of print]