Sequential Regimen of Bendamustine Followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in Patients With Relapsed/Refractory CLL (CLL2-BZAG)
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|ClinicalTrials.gov Identifier: NCT04515238|
Recruitment Status : Recruiting
First Posted : August 17, 2020
Last Update Posted : October 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphoid Leukemia||Drug: Bendamustine Biological: Obinutuzumab Biological: Zanubrutinib Biological: Venetoclax||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of a Sequential Regimen of Bendamustine Followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in Patients With Relapsed/Refractory CLL (CLL2-BZAG Protocol)|
|Actual Study Start Date :||October 1, 2020|
|Estimated Primary Completion Date :||October 2022|
|Estimated Study Completion Date :||September 2025|
Debulking: 2 debulking cycles (q 28d) of bendamustine will be administered unless the patient has a contraindication or a debulking is not clinically indicated
Induction: 6 cycles (q 28d) of Obinutuzumab + Zanubrutinib + Venetoclax
Maintenance: max. 8 cycles (q 84d) of Obinutuzumab + Zanubrutinib + Venetoclax
Maintenance treatment will be continued until (whichever occurs first):
Debulking: Cycles 1-2: d1+2 - 70mg/m² i.v.
Induction: Cycle 1: d1 - 100 mg, d1 (or d2) - 900 mg, d8 + d15 - 1000 mg i.v.; Cycle 2 - 6: 1000 mg, d1 i.v.
Maintenance: Cycle 1 - 8: 1000 mg, d1 i.v.
Induction: Cycle 1: --; Cycles 2 - 6: d1-28: 2 x 160mg p.o.
Maintenance: Cycle 1 - 8: d1-84: 2 x 160mg p.o
Other Name: BGB-3111
Induction: Cycles 1 + 2: --; Cycle 3: d1-7: 20mg, d8-14: 50mg, d15-21: 100mg, d22-28: 200mg p.o.; Cycle 4 - 6: d1-28: 400 mg p.o.
Maintenance: Cycle 1 - 8: d1-84: 400 mg p.o.
- Negativity rate of minimal residual disease (MRD) in peripheral blood (PB) measured by multi-color flow cytometry [ Time Frame: At final restaging (RE): 12 weeks after the start of the last induction cycle ]MRD negativity is defined as less than one (1) CLL-cell among 10,000 leukocytes analyzed [0.01%]. The MRD negativity rate is defined as the proportion of patients having achieved MRD negativity based on the full analysis set (FAS).
- Overall response rate (ORR) [ Time Frame: At final restaging (RE): 12 weeks after the start of the last induction cycle ]Proportion of patients having achieved a complete response (CR), a CR with incomplete recovery of the bone marrow (CRi), or a partial response (PR) as best response.
- CR / CRi rate [ Time Frame: At final restaging (RE): 12 weeks after the start of the last induction cycle ]Proportion of patients having achieved a CR or CRi as best response (= number of patients with best response CR or CRi divided by the number of the FAS)
- MRD in PB measured by 4-color flow cytometry at different times to guide the duration of maintenance therapy and for the assessment of the kinetics of response to the different treatment phases [ Time Frame: From date of screening until the end of follow-up, up to 55 month ]MRD negativity is defined as less than one (1) CLL-cell among 10,000 leukocytes analyzed [0.01%], i.e. < 10-4. MRD values will be categorized into negative (<10-4) and positive (≥10-4)
- Safety: Adverse events (AE), serious adverse events (SAE) and adverse events of particular/special interest (AEPI/AESI) [ Time Frame: Up to 55 months after first dose of study drug ]Type, frequency, severity and relationship to study treatment.of AEs, SAEs and AEPIs/AESIs
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04515238
|Contact: Paula Cramer, Dr. med.||+49 221 478 firstname.lastname@example.org|
|Contact: Moritz Fürstenau, Dr. med.||+49 221 478 email@example.com|
|Universitaetsklinikum Schleswig-Holstein Campus Kiel||Recruiting|
|Kiel, Germany, 24105|
|Ulm, Germany, 89070|
|Principal Investigator:||Paula Cramer, Dr. med.||German CLL Study Group|