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| Title | A prospective, open-label, multicenter phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by GA101 and ibrutinib (BIG) followed by GA101 and ibrutinib maintenance in CLL patients |
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| Protocol IDs | EudraCT: 2014-000569-35 NCT02345863 |
| Participating Countries | Germany |
| Status | completed |
| Contact | DCLLSG Office: Tel. +49 (0) 221-478-88220 |
| Design | Prospective, multicenter, single-arm, open-label phase-II trial |
| 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, AESI and their relationship to study treatment - MRD levels measured in peripheral blood - Best response rate (BRR) until 6 months after RE - ORR after debulking, maintenance therapy,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) complete response rate (CR) - 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 according to iwCLL criteria, requiring treatment - Previously untreated or relapsed/refractory CLL - Fit and unfit patients - ECOG performance status 0 – 2 - 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 |
| Induction GA101 (Obinutuzumab) i.v. Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg Cycle 2 - 6: 1000 mg, d1 + Ibrutinib p.o. Cycle 2 - 6: 420 mg daily |
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| Maintenance GA101 (Obinutuzumab) i.v. Cycle 1 - 8: 1000 mg, d1 Ibrutinib p.o. Cycle 1 - 8: 420 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 |
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| Patients recruited | 66 patients |
| Time schedule | Recruitment period: 16 Jan 2015 - 31 Aug 2015 End of study: Mar 2019 Clinical Study Report / Publication: scheduled for Mar 2020 End of archiving period: Mar 2029 |
| Sponsor | University of Cologne |
| Principal Investigator | Dr. med. Julia von 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. von Tresckow J, Cramer P, Bahlo J, Robrecht S, Langerbeins P, Fink AM, Al-Sawaf O, Illmer T, Klaproth H, Estenfelder S, Ritgen M, Fischer K, Wendtner CM, Kreuzer KA, Stilgenbauer S, Böttcher S, Eichhorst BF, Hallek M CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia Leukemia. 2019 May;33(5):1161-1172 doi: 10.1038/s41375-018-0313-8 |