DCLLSG

CLL2-BAAG 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), acalabrutinib (ACP-196) and ABT-199 (venetoclax) in patients with relapsed/refractory CLL
Protocol IDs EudraCT: 2017-003133-28
NCT03787264
Participating Countries Germany
Status in follow up
Contact Medical Management: Dr. Paula Cramer

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

Project Management: Berit Falkowski

Berit Falkowski
+49 221 478-96581
berit.falkowski@uk-koeln.de

Data Management: Olga Korf

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

Safety Management: Tanja Annolleck

Tanja Annolleck
+49 221 478-96579
tanja.annolleck@uk-koeln.de

Contact for scientific queries Dr. Paula Cramer

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

Dr. Moritz Fürstenau

Dr. Moritz Fürstenau
+49 221 478-96121
moritz.fuerstenau@uk-koeln.de

Design Prospective, multicenter, single-arm, open-label, phase-II trial
Primary Endpoint Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by 4-color flow cytometry at final restaging (RE)
Secondary Endpoints – Overall response rate (ORR) at RE, including all patients achieving:
   · a complete response (CR),
   · CR with incomplete recovery of the bone marrow (CRi), or
   · a partial response (PR).
– CR / CRi rate at RE
– Differentiation of patients with a PR according to iwCLL crite-ria into patients achieving:
   · an unconfirmed (clinical) CR/CRi lacking a CT/MRI scan and/or a bone marrow biopsy
   · a PR due to residual lymphadenopathy and/or hepatosplenomegaly, or
   · a PR due to residual bone marrow infiltration
– Safety parameters: adverse events (AE), serious adverse events (SAE) and adverse events of particular interest (AEPI)
– MRD in PB measured by 4-color flow cytometry to guide the duration of maintenance therapy at:
   · RE 12 weeks after the start of the last cycle of induc-tion therapy in all patients responding to study treat-ment and
   · every 12 weeks (= approx. 3 months) during the maintenance phase.every 24 weeks (= approx. 6 months) during the follow-up
– and MRD in PB measured by 4-color flow cytometry for the assessment of the kinetics of response to the different treatment phases at:
   · screening/baseline
   · staging after debulking (if applicable)
   · before start with acalabrutinib (cycle 2, d1)
   · before start with venetoclax (cycle 3, d1)
   · interim staging (after 3 induction cycles)
   · initial response assessment (after 6 induction cycles)
– MRD in bone marrow measured by 4-color flow cytometry op-tionally in patients with (clin.) CR/CRi (or PR almost fulfilling CR criteria, e.g. with residual splenomegaly) 12 weeks after achievement of MRD negativity in PB
– Best response rate (BRR) until 6 months after RE
– ORR after debulking and after end of maintenance treatment
– Progression-free survival (PFS)
– Event-free survival (EFS)
– Overall survival (OS)
– Duration of response in patients with a complete response (CR), a CR with incomplete recovery of the bone marrow (CRi), a partial remission (PR) (including patients with a PR due to residual lymphadenopathy and/or hepatosplenomegaly or due to residual bone marrow infiltration as well as patients with an unconfirmed (clinical) CR/CRi lacking a CT/MRI scan and/or a bone marrow biopsy)
– Treatment-free survival (TFS) and time to next CLL treatment (TTNT)
Target Population Relapsed/refractory CLL in need of treatment according to iwCLL criteria
- Creatinine clearance ≥30ml/minL
- ECOG performance status 0 – 2 (ECOG 3 only permitted if related to CLL)
- Age  ≥ 18 years
Treatment Debulking
2 debulking cycles (q 28d) 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
Induction
6 cycles, q 28d
Obinutuzumab
(GA101) i.v.
Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg
Cycle 2 - 6: 1000 mg, d1
+ Acalabrutinib (ACP-196) p.o.
Cycle 1: --
Cycles 2 - 6: d1-28: 2 x 100mg
+ Venetoclax (ABT-199) p.o.
Cycles 1 + 2: --
Cycle 3: d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg
Cycle 4 - 6: d1-28: 400 mg
Maintenance
max. 8 cycles, q 84d
Obinutuzumab i.v.
Cycle 1 - 8: 1000 mg, d1
+ Acalabrutinib (ACP-196) p.o.
Cycle 1 - 8: d1-84: 2 x 100mg
+ Venetoclax p.o.
Cycle 1 - 8: d1-84: 400 mg

Maintenance treatment will be continued until (whichever occurs first):
- 12 weeks (approx. 3 months) after confirmation of achievement of a CR/CRi and MRD negativity
- maintenance cycle 8
- progression of CLL or start of a subsequent therapy
- unacceptable toxicity
Patients recruited 46 patients
Time schedule Recruitment period: 14 Jan 2019 - 25 Jun 2020
End of trial Q3/2023
Protocol Version 06 Nov 2018 Protocol (Version 1.2)
26 Nov 2019 Amendment 1 (Version 2.0)
Sponsor University of Cologne
Principal Investigator Dr. med. Paula Cramer, Department I of Internal Medicine, Cologne University Hospital
Documents
(publicly available)
Synopsis (Version 2.0 | 26 Nov 2019)
Documents
(password protected)
Protocol and other documents see Download Center