Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab + Venetoclax (RVe) Versus Obinutuzumab (GA101) + Venetoclax (GVe) Versus Obinutuzumab + Ibrutinib + Venetoclax (GIVe) in Fit Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation

Sponsor
German CLL Study Group
Study ID
NCT02950051
Phase
PHASE3
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Fludarabine — DRUG
    Fludarabine i.v.: cycles 1-6: 25 mg/m², d1-3, q28d
  • Cyclophosphamide — DRUG
    Cyclophosphamide i.v.: cycles 1-6: 250 mg/m², d1-3, q28d
  • Rituximab — BIOLOGICAL
    Rituximab i.v. (before chemotherapy): cycle 1: 375 mg/m², d0; cycles 2-6: 500 mg/m², d1; q28d
  • Bendamustine — DRUG
    Bendamustine i.v.: cycles 1-6: 90mg/m², d1-2, q28d
  • Venetoclax — DRUG
    Venetoclax p.o. (ramp-up: dose escalation until final dose is reached) cycle 1: 20 mg (2 tabl. at 10 mg), d22-28, q28d cycle 2: 50 mg (1 tabl. at 50 mg), d1-7; 100 mg (1 tabl. at 100 mg), d8-14; 200 mg (2 tabl. at 100 mg), d15-21; 400 mg (4 tabl. at 100 mg), d22-28, q28d cycles 3-12: 400 mg (4 tabl. at 100 mg), d1-28, q28d
  • Obinutuzumab — BIOLOGICAL
    Obinutuzumab i.v. cycle 1: 100 mg, d1; 900 mg, d1(2); 1000 mg, d8+15, q28d cycles 2-6: 1000 mg, d1, q28d
  • Ibrutinib — DRUG
    Ibrutinib p.o. cycles 1-12: 420 mg, d1-28, q28d cycles 13-36: 420 mg, d1-28, q28d

Study Details

The aim of this study is to evaluate if standard chemoimmunotherapy (FCR, BR) in frontline treatment of physically fit CLL patients without del17p or TP 53 mutation can be replaced by combinations of targeted drugs (Venetoclax, Ibrutinib) with anti-CD20-antibodies (Rituximab, Obinutuzumab), which may induce extremely long lasting remissions.

Key Dates

Start date
Dec 13, 2016
Status verified
Mar 2024
Primary completion
Feb 29, 2024
Completion
Feb 29, 2024

Study Design

Enrollment
926 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Standard chemoimmunotherapy (SCIT)
    Patients up to age 65: 6 cycles (q28d) of Fludarabine + Cyclophosphamide + Rituximab (FCR) Patients older than 65 years: 6 cycles (q28d) of Bendamustine + Rituximab (BR)
  • Experimental: Rituximab + Venetoclax (RVe)
    6 cycles (q28d) of RVe + 6 cycles (q28d) of Venetoclax (alone)
  • Experimental: Obinutuzumab + Venetoclax (GVe)
    6 cycles (q28d) of GVe + 6 cycles (q28d) of Venetoclax (alone)
  • Experimental: Obinutuzumab + Ibrutinib + Venetoclax (GIVe)
    6 cycles (q28d) of GIVe + 6 cycles (q28d) of Ibrutinib plus Venetoclax. Administration of ibrutinib will be continued for a maximum of 36 months or until MRD negativity, start of new anti-CLL therapy or inacceptable toxicity, whatever occurs first.

Primary Outcome Measure

Miminimal residual disease (MRD) negativity rate in peripheral blood (PB) [ Time Frame: Month 15 ]

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