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 followed by Ibrutinib and GA101 maintenance in CLL patients.
In the CLL2-BIG trial an allcomer CLL population with indication for treatment will be included. Patient will receive 2 cycles of debulking treatment with bendamustin unless contraindications are existing or debulking is not indicated. Afterwards 6 cycles of induction therapy with GA101 and ibrutinib will be applied, each with a duration of 28 days. Primary endpoint overall Response rate will be assessed at final restaging. Patients benefitting from BIG treatment will enter the maintenance phase of the trial. Maintenance treatment will be continued if no unacceptable toxicity occurs until three months after negativity of minimal residual disease \[MRD\] is achieved in peripheral blood in patients with (clinical) complete response (CR) or (clinical) incomplete complete response \[CRi\] (confirmed by 2 consecutive testings of MRD within 3 months), progression of CLL, start of a subsequent therapy or up to 8 cycles of maintenance (each cycle with a duration of 84 calendar days = 3 months), whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Debulking: 2 cycles of Bendamustine (70 mg/m² iv) will be administered before induction unless a contraindication is existing or it is not clinically indicated.
Induction GA101 iv infusion: Cycle 1: Day 1 100 mg Day 1 (or 2) 900 mg Day 8 1000 mg Day 15 1000 mg Cycle 2-6: Day 1 1000 mg Maintenance After the induction ibrutinib po 420 mg daily and GA101 iv 1000 mg every three months will be continued. GA101: Cycle 1-8 Day 1 1000 mg
Ibrutinib will be administered as a daily oral dosage of 420 mg starting on cycle 2 day 1. Cycle 2-6: Day 1 420 mg daily Maintenance After the induction ibrutinib po 420 mg daily and GA101 iv 1000 mg every three months will be continued. Ibrutinib: Cycle 1-8 420 mg daily
German CLL Study Group
Cologne, Germany
Overall response rate (ORR)
proportion of patients responding according to international working Group on chronic lymphocytic leukemia criteria
Time frame: 84 days after first dose of last induction cycle
Safety: Adverse events (AEs) and adverse events of special interest (AESI)
Type, frequency, and severity of adverse events (AEs) and adverse events of special interest (AESI) and their relationship to study treatment.
Time frame: up to 48 months after first dose of study drug
minimal residual disease (MRD)
Rate of MRD responses in peripheral blood measured by immunophenotyping
Time frame: final restaging and during maintenance
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