CLLRUmbrella2 Trial

Title A Prospective, Randomized, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of GS-4059 and Entospletinib with and without Obinutuzumab in Subjects with Chronic Lymphocytic Leukemia
Protocol IDs EudraCT: 2016-002768-15
Status in follow up
General Inquiries cll-umbrella@uk-koeln.de
Contact Medical Management: Dr. Nadine Kutsch

Dr. Nadine Kutsch
+49 221 478-88192

Project Management: Aline Zey

Aline Zey
+49 221 478-96577

Contact for scientific queries Prof. Dr. Barbara Eichhorst

Prof. Dr. Barbara Eichhorst
+49 221 478-88155 (Office)

Design Prospective, open-label, randomized, multicenter phase 2 study
Primary Endpoint Rate of complete remission (CR) according to the IWCLL guidelines at Week 25
Secondary Endpoints - Rate of complete response (CR) with bone marrow minimal residual disease (MRD) negativity (CR/BM MRD-) at Week 25
- Rate of CR with MRD negativity (<10-4) in peripheral blood (CR/PB MRD-) at Week 25
- Overall response rate (ORR) at Week 25
- Progression-free survival (PFS)
- Type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs)
Study Population - Relapsed or refractory CLL
- Requiring treatment per modified IWCLL 2008 criteria AND radiographically measureable disease (CT, MRI)
- no prior therapy with any inhibitor of BTK, SYK, PI3K, BCL-2 or obinutuzumab
- Age  ≥ 18 years
Treatment Arm A (GS-4059 + Entospletinib)
up to 104 weeks
GS-4059 p.o.: 80 mg daily
Entospletinib p.o.: 400 mg daily
Arm B (GS-4059 + Entospletinib + Obinutuzumab)
up to 104 weeks
GS-4059 p.o.: 80 mg daily
Idelalisib p.o.: 400 mg daily
Entospletinib i.v.
6 cycles, q 28d (= 21 weeks)
Cycle 1: (100 mg, d1 + 900 mg, d2) or 1000 mg, d1; 1000 mg, d8 + d15
Cycle 2 - 6: 1000 mg, d1
Patients recruited 36 patients
Time schedule Recruitment period:: 06 April 2017 - 04 September 2018
End of Study: Q1/2023
Protocol Version Protocol (25 August 2016)
Amendment 1 (16 November 2016)
Sponsor Gilead Sciences, Inc.
Principal Investigator Prof. Dr. Barbara Eichhorst, Dept. Internal Medicine I, University Hospital of Cologne
Coordinating Physician Dr. Nadine Kutsch, Dept. Internal Medicine I, University Hospital of Cologne
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Access only with personal username and password, which have been sent to the study centers.