DCLLSG

CLL2-BIO Trial

Title A prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by ofatumumab and ibrutinib followed by ibrutinib and ofatumumab maintenance in CLL patients
Protocol IDs EudraCT: 2014-000590-39
NCT02689141
Status completed
Contact DCLLSG Office: Tel. +49 (0) 221-478-88220
Design Prospective, multicenter, single-arm, open-label phase-II trial
Objective Evaluation of the efficacy and safety of the therapeutic regimen
Primary Endpoint Overall response rate (ORR) at final restaging (RE) including all patients achieving CR, CRi, PR or PR with lymphocytosis
Secondary Endpoints - Safety parameters: AEs, AESIs and their relationship to study treatment
- MRD levels in peripheral blood
- Optional: MRD level in bone marrow in patients with (clinical) CR or CRi
3 months after achievement of MRD negativity in peripheral blood
- Best response rate (BRR) until 6 months after RE
- ORR after debulking, after end of maintenance treatment, in the two strata of previously untreated and relapsed/refractory patients, as well as in the fit and unfit patients for all response definitions, in biological defined risk groups
- (Clinical) CR / CRi rate
- Progression-free survival (PFS)
- Event-free survival (EFS)
- Overall survival (OS)
- Duration of response, treatment free survival and time to next treatment
- Evaluation of relationship between various baseline markers and clinical outcome parameters
Target Population - B-CLL requiring treatment according to iwCLL criteria
- 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 cycles; q 28d (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
Ofatumumab i.v.
Cycle 1: d1 - 300 mg, d8 + d15 - 1000 mg
Cycle 2 - 6: 1000 mg, d1
Ibrutinib p.o.
Cycle 1: --
Cycle 2 - 6: 420 mg (3 tabl.) daily

During the phase of staging between induction and maintenance the intake of Ibrutinib is continued.
Maintenance
Max. 8 cycles, q 84d
Ofatumumab i.v.
Cycle 1 - 8: 1000 mg, d1
Ibrutinib p.o.
Cycle 1 - 8: 420 mg (3 tabl.) daily

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
Enrollment 66 patients
Time schedule Recruitment period: 04 February 2016 - 04 October 2016
End of study: February 2020
Clinical study report: scheduled for February 2021
End of archiving period: February 2030
Sponsor University of Cologne
Global Principal Investigator Dr. med. Paula Cramer, Department I of Internal Medicine, University Hospital of Cologne
Coordinating Physician Dr. med. Julia v. Tresckow, Department I of Internal Medicine, University Hospital of Cologne
Publications Cramer P, Tausch E, von Tresckow J, Giza A, Robrecht S, Schneider C, Fürstenau 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 Jun 4 blood.2020010484. doi: 10.1182/blood.2020010484. Online ahead of print.

Cramer P, V Tresckow J, Robrecht S, Bahlo J, Fürstenau M, Langerbeins P, Pflug N, Al-Sawaf O, Heinz WJ, Vehling-Kaiser U, Dürig J, Tausch E, Hensel M, Sasse S, Fink AM, Fischer K, Kreuzer KA, Böttcher S, Ritgen M, Kneba M, Wendtner CM, Stilgenbauer S, Eichhorst B, Hallek M
Bendamustine, followed by ofatumumab and ibrutinib in chronic lymphocytic leukemia (CLL2-BIO): primary endpoint analysis of a multicentre, open-label phase-II trial
Haematologica. 2020 Feb 27. pii: haematol.2019.223693. doi: 10.3324/haematol.2019.223693. [Epub ahead of print]