A Study to Evaluate the Benefit of Venetoclax Plus Rituximab Compared With Bendamustine Plus Rituximab in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
CompletedPhase 3Results postedLast updated 17 October 2023
What this trial tests
Phase 3 trial testing Bendamustine in Chronic Lymphocytic Leukemia in 389 participants. Completed in 3 August 2022.
18 and older, any sex, with Chronic Lymphocytic Leukemia. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or DeathPrimary· Baseline up to PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)
Assessment of response was performed by the investigator according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (greater than \[\>\] 1.5 centimeters \[cm\]); unequivocal progression of non-target lesion; an increase of greater than or equal to (\>/=) 50 percent (%) compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count \>/=5000 per microliter (mcL), or in longest diameter of any extra nodal lesion; transformation to a more aggressive histolog
Group
Value
95% CI
Bendamustine + Rituximab Main Study
88.7
Venetoclax + Rituximab Main Study
70.1
Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL GuidelinesPrimary· Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the investigator using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; increase of \>/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count \>/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of \>/=50% in platelet or neutrophil count, or hemoglobin level by \>2 g/dL or to \<10 g/dL. Pa
Group
Value
95% CI
Bendamustine + Rituximab Main Study
17.0
15.5 – 21.7
Venetoclax + Rituximab Main Study
54.7
52.3 – 59.9
Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL GuidelinesSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Assessment of response was performed by the IRC according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; an increase of \>/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count \>/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of \>/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglo
Group
Value
95% CI
Bendamustine + Rituximab Main Study
54.4
Venetoclax + Rituximab Main Study
18.0
PFS as Assessed by the IRC Using Standard iwCLL GuidelinesSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the IRC using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; increase of \>/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count \>/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of \>/=50% in platelet or neutrophil count, or hemoglobin level by \>2 g/dL or to \<10 g/dL. Participant
Group
Value
95% CI
Bendamustine + Rituximab Main Study
18.1
15.8 – 22.3
Venetoclax + Rituximab Main Study
NA
NA – NA
Percentage of Participants With PD or Death as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by Fluorescence In-situ Hybridization (FISH) TestSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
Assessment of response was performed by the investigator according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; an increase of \>/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count \>/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of \>/=50% compared to baseline in platelet or neutrophil count; or decrease i
Group
Value
95% CI
Bendamustine + Rituximab 17p Del. Population
80.4
Venetoclax + Rituximab 17p Del. Population
80.4
PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH TestSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the investigator using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; increase of \>/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count \>/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of \>/=50% in platelet or neutrophil count, or hemoglobin level by \>2 g/dL or to \<10 g/dL. Pa
Group
Value
95% CI
Bendamustine + Rituximab 17p Del. Population
15.4
10.0 – 21.0
Venetoclax + Rituximab 17p Del. Population
47.9
37.4 – 59.9
Percentage of Participants With PD or Death as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH TestSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
Assessment of response was performed by the IRC according to the iwCLL guidelines. PD was defined as occurrence of one of the following events: appearance of any new extra nodal lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; an increase of \>/=50% compared to baseline in splenomegaly, hepatomegaly, number of blood lymphocytes with lymphocyte count \>/=5000/mcL, or in longest diameter of any extra nodal lesion; transformation to a more aggressive histology; decrease of \>/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglo
Group
Value
95% CI
Bendamustine + Rituximab 17p Del. Population
47.8
Venetoclax + Rituximab 17p Del. Population
19.6
PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH TestSecondary· Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
PFS was defined as the time from randomization until first occurrence of PD/relapse as assessed by the IRC using iwCLL guidelines, or death from any cause, whichever occurred first. PD: occurrence of one of the following: new lesion; new palpable lymph node (\>1.5 cm); unequivocal progression of non-target lesion; increase of \>/=50% in splenomegaly, hepatomegaly, blood lymphocytes with count \>/=5000/mcL, longest diameter of any lesion; transformation to more aggressive histology; decrease of \>/=50% in platelet or neutrophil count, or hemoglobin level by \>2 g/dL or to \<10 g/dL. Participant
Group
Value
95% CI
Bendamustine + Rituximab 17p Del. Population
16.1
13.6 – 22.3
Venetoclax + Rituximab 17p Del. Population
NA
27.6 – NA
Percentage of Participants With Best Overall Response of Complete Response (CR), CR With Incomplete Bone Marrow Recovery (CRi), Nodular Partial Response (nPR), or Partial Response (PR) as Assessed by the Investigator Using iwCLL GuidelinesSecondary· Baseline up to approximately 8 years 5 months
Response was assessed by investigator according to iwCLL guidelines and was confirmed by repeat assessment \>/=4 weeks after initial documentation. CR: peripheral blood lymphocytes \<4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with \<30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: \>/=50% reduction in two of f
CR
Group
Value
95% CI
Bendamustine + Rituximab Main Study
8.2
4.76 – 12.98
Venetoclax + Rituximab Main Study
26.3
20.24 – 33.07
CRi
Group
Value
95% CI
Bendamustine + Rituximab Main Study
0.5
0.01 – 2.82
Venetoclax + Rituximab Main Study
1.5
0.32 – 4.45
nPR
Group
Value
95% CI
Bendamustine + Rituximab Main Study
6.2
3.22 – 10.50
Venetoclax + Rituximab Main Study
3.6
1.46 – 7.29
PR
Group
Value
95% CI
Bendamustine + Rituximab Main Study
52.8
45.56 – 59.99
Venetoclax + Rituximab Main Study
61.9
54.62 – 68.72
Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL GuidelinesSecondary· Baseline up to last FUV (up to approximately 3 years)
Response was assessed by IRC according to iwCLL guidelines and was confirmed by repeat assessment \>/=4 weeks after initial documentation. CR: peripheral blood lymphocytes \<4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, constitutional symptoms; neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with \<30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: \>/=50% reduction in 2 of following: perip
Group
Value
95% CI
Bendamustine + Rituximab Main Study
67.7
60.64 – 74.20
Venetoclax + Rituximab Main Study
93.3
88.81 – 96.38
Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the Investigator Using iwCLL GuidelinesSecondary· End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days
Response was assessed by investigator according to iwCLL guidelines and was confirmed by repeat assessment \>/=4 weeks after initial documentation. CR: peripheral blood lymphocytes \<4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with \<30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: \>/=50% reduction in 2 of fol
Group
Value
95% CI
Bendamustine + Rituximab Main Study
63.1
55.89 – 69.86
Venetoclax + Rituximab Main Study
88.1
82.74 – 92.33
Percentage of Participants With Overall Response of CR, Cri, nPR, or PR at End of Combination Treatment Visit as Assessed by the IRC Using iwCLL GuidelinesSecondary· EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
Response was assessed by the IRC according to the iwCLL guidelines and was confirmed by repeat assessment \>/=4 weeks after initial documentation. CR: peripheral blood lymphocytes \<4000/mcL; absence of any new lesion, nodal disease, lymphadenopathy, hepatomegaly, splenomegaly, and constitutional symptoms; neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL without need for transfusion or exogenous growth factors; normocellular bone marrow with \<30% lymphocytes; no lymphoid nodules. CRi: fulfilling all CR criteria but persistent cytopenia. PR: \>/=50% reduction in two of th
Group
Value
95% CI
Bendamustine + Rituximab Main Study
62.6
55.37 – 69.37
Venetoclax + Rituximab Main Study
87.1
81.57 – 91.48
Adverse events — posted to ClinicalTrials.gov
Time frame: From signing of informed consent form up to approximately 8 years 5 months.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Bendamustine + Rituximab Main Study
Serious: 84/188 (45%)
Deaths: 84/188
Venetoclax + Rituximab Main Study
Serious: 101/194 (52%)
Deaths: 60/194
Bendamustine + Rituximab Crossover Substudy
Serious: 5/9 (56%)
Deaths: 1/9
Venetoclax + Rituximab Re-Treatment Substudy
Serious: 13/25 (52%)
Deaths: 8/25
Serious adverse events (167 terms)
Reaction
System
Bendamustine + Rituximab M…
Venetoclax + Rituximab Mai…
Bendamustine + Rituximab C…
Venetoclax + Rituximab Re-…
Pneumonia
Infections and infestations
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Febrile neutropenia
Blood and lymphatic system disorders
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Pyrexia
General disorders
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Infusion related reaction
Injury, poisoning and procedural complications
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Anaemia
Blood and lymphatic system disorders
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Hypotension
Vascular disorders
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Sepsis
Infections and infestations
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Upper respiratory tract infection
Infections and infestations
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Tumour lysis syndrome
Metabolism and nutrition disorders
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Autoimmune haemolytic anaemia
Blood and lymphatic system disorders
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Neutropenia
Blood and lymphatic system disorders
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Influenza
Infections and infestations
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Lung neoplasm malignant
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
The purpose of this open-label, multicenter, randomized, Phase III study is to evaluate the benefit of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in participants with relapsed or refractory CLL. Participants will be randomly assigned in 1:1 ratio to receive either venetoclax + rituximab (Arm A) or bendamustine + rituximab (Arm B).
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT07225985 — Pralatrexate With Bendamustine and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Re
· Phase 1, PHASE2
· not yet recruiting
NCT07189065 — A Study of Rocbrutinib in Participants With Relapse or Refractory Non-GCB Diffuse Large B-Cell Lymphoma
· Phase 2
· recruiting
NCT07169565 — Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
· Phase 1
· not yet recruiting
NCT06911502 — A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Ch
· Phase 3
· recruiting
NCT07003464 — Phase II Trial of Zanubrutinib, Obinutuzumab, Bendamustine (ZGB) as First-Line Therapy for Chronic Lymphocytic Leukemia:
· Phase 2
· not yet recruiting
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NCT07014917 — Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL
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Publications: Europe PMC API search by NCT ID, retrieved 9 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Hoffmann-La Roche
Last refreshed: 17 October 2023
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02005471.