TriangleNCT02005471 · CITED IN SOURCE DOCUMENTS
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)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2023-10-17
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).
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death
Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines
Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL Guidelines
PFS as Assessed by the IRC Using Standard iwCLL Guidelines
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) Test
PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
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 Test
PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
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 Guidelines
Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL Guidelines
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 Guidelines
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 Guidelines
Percentage of Participants Who Died
Overall Survival (OS)
Percentage of Participants With PD/Relapse, Start of a New Anti-Chronic Lymphocytic Leukemia (CLL) Therapy, or Death as Assessed by the Investigator Using iwCLL Guidelines
Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines
Percentage of Participants With PD or Death Among Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the Investigator Using iwCLL Guidelines
Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines
Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator
Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator
Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood
Percentage of Participants With MRD Negativity in Bone Marrow
Plasma Venetoclax Concentrations
Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores
Change From Baseline in HRQoL as Measured by European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Functional Scales Score and Global Health Status/Global Quality-of-Life (QoL) Scale Score
Change From Baseline in HRQoL as Measured by Quality of Life Questionnaire Associated CLL Module (QLQ-CLL16) Multi-Item Scales Score
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of Participants With Grade 3 or Higher Tumor Lysis Syndrome (TLS) and Infusion-related Reactions (IRRs)
Change From Baseline in Lymphocyte Subset Counts at Specified Time Points
Euro QoL 5 Dimension (EQ-5D) Questionnaire Score
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Diagnosis of CLL per diagnostic criteria for relapsed or refractory CLL per the international workshop on chronic lymphocytic leukemia (iwCLL) guidelines * Previously treated with 1-3 lines of therapy (example: completed greater than or equal to \[\>/=\] 2 treatment cycles per therapy), including at least one standard chemotherapy-containing regimen * Participants previously treated with bendamustine only if their duration of response was \>/= 24 months * Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 1 * Adequate bone marrow function * Adequate renal and hepatic function * Participants must use effective birth control throughout study until at least 30 days after study treatment or 1 year after rituximab treatment, whichever is later; female participants must not be pregnant or breast-feeding * For participants with the 17p deletion, previously treated with 1-3 lines of therapy, including at least one prior standard chemotherapy-containing regimen or at least one prior alemtuzumab-containing therapy Inclusion Criteria R/C Substudy: * Participants randomized to Arm A or Arm B with a confirmed disease progression of CLL per iwCLL criteria * Participants who have not received new anti-CLL therapy following disease progression in Arm A or Arm B * Adequate renal and hepatic function per laboratory reference range Exclusion Criteria: * Transformation of CLL to aggressive non-Hodgkin lymphoma or central nervous system (CNS) involvement by CLL * Undergone an allogenic stem cell transplant * A history of significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular or hepatic disease * Hepatitis B or C or known human immunodeficiency virus (HIV) positive * Receiving warfarin treatment * Received an anti-CLL monoclonal antibody within 8 weeks prior to the first dose of study drug * Received any anti-cancer or investigational therapy within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy * Received cytochrome P450 3A4 (CYP3A4) inhibitors (such as fluconazole, ketoconazole and clarithromycin) or inducers (such as rifampin, carbamazapine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax * History of prior venetoclax treatment * Participants with another cancer, history of another cancer considered uncured on in complete remission for \<5 years, or currently under treatment for another suspected cancer except non-melanoma skin cancer or carcinoma in situ of the cervix that has been treated or excised and is considered resolved * Malabsorption syndrome or other condition that precludes enteral route of administration * Other clinically significant uncontrolled condition(s) including, but not limited to, systemic infection (viral, bacterial or fungal) * Vaccination with a live vaccine within 28 days prior to randomization * Consumed grapefruit or grapefruit products, seville oranges (including marmalade containing seville oranges), or star fruit within 3 days prior to the first dose of study treatment * A cardiovascular disability status of New York Heart Association Class \>/=3. Class 3 is defined as cardiac disease in which participants are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnea, or anginal pain * Major surgery within 30 days prior to the first dose of study treatment * A participant who is pregnant or breastfeeding * Known allergy to both xanthine oxidase inhibitors and rasburicase Exclusion Criteria R/C Substudy: * Transformation of CLL to aggressive NHL (e.g., Richter's transformation, prolymphocytic leukemia, or DLBCL) or CNS involvement by CLL * Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) * Development of other malignancy since enrollment into the study, with the exception of curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia * History of severe (i.e., requiring permanent discontinuation of prior rituximab therapy) prior allergic or anaphylactic reactions to rituximab * Known HIV positivity * Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HbsAg\] serology) * Positive test results for hepatitis C virus (HCV; HCV antibody serology testing) * Requires the use of warfarin (due to potential drug interactions that may potentially increase the exposure of warfarin) * Has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(ies) of any previous therapy * Received potent CYP3A4 inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of study treatment * Received potent CYP3A4 inducers (such as rifampin, carbamazepine, phenytoin, St. John's wort) within 7 days prior to the first dose of study treatment * Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study treatment * A cardiovascular disability status of New York Heart Association Class \>/= 3 * A significant history of renal, neurologic, psychiatric, endocrine, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the investigator, would adversely affect the participants's participation in this study or interpretation of study outcomes * Major surgery within 30 days prior to the first dose of study treatment * A participant who is pregnant or breastfeeding * Malabsorption syndrome or other condition that precludes enteral route of administration * Known allergy to both xanthine oxidase inhibitors and rasburicase * Vaccination with a live vaccine within 28 days prior to randomization
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive bendamustine 70 milligrams per meter square (mg/m\^2) via intravenous (IV) infusion on Days 1 and 2 of each 28-day cycle for 6 cycles, in combination with rituximab 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.
- intervention Names
- Drug: Bendamustine
- Drug: Rituximab
- label
- Bendamustine + Rituximab
- type
- ACTIVE_COMPARATOR
- description
- Participants will be initially placed on a venetoclax 5 weeks ramp-up period, and will receive an initial dose of 20 milligrams (mg) via tablet orally once daily (QD). Then the dose will be incremented weekly up to a maximum dose of 400 mg. Participants will then continue receiving venetoclax 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards, as directed by the investigator, in combination with rituximab 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.
- intervention Names
- Drug: Venetoclax
- Drug: Rituximab
- label
- Venetoclax + Rituximab
- type
- EXPERIMENTAL
- description
- Participants entering the Crossover Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Crossover Day 1 of the Substudy.
- intervention Names
- Drug: Venetoclax
- Drug: Rituximab
- label
- Bendamustine + Rituximab Crossover Substudy
- type
- EXPERIMENTAL
- description
- Participants entering the Re-Treatment Substudy will have a 5-week venetoclax dose ramp-up period to reach the target dose of 400 mg QD. Following the venetoclax ramp-up period, Participants will receive 6 cycles of rituximab consisting of a single infusion on the first day of each 28-day cycle. Participants will continue to take their daily dose of venetoclax during the rituximab cycles. Participants who have not progressed following the completion of the 6 cycles will continue to receive venetoclax monotherapy until disease progression or for a maximum of 2 years from Cycle 1 Re-Treatment Day 1 of the Substudy.
- intervention Names
- Drug: Venetoclax
- Drug: Rituximab
- label
- Venetoclax + Rituximab Re-Treatment
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Bendamustine + Rituximab
- description
- Bendamustine will be administered at a dose of 70 mg/m\^2 via IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.
- name
- Bendamustine
- type
- DRUG
- arm Group Labels
- Bendamustine + Rituximab Crossover Substudy
- Venetoclax + Rituximab
- Venetoclax + Rituximab Re-Treatment
- description
- Venetoclax will be administered at an initial dose of 20 mg via tablet orally QD, incremented weekly up to a maximum dose of 400 mg during a 5-week ramp-up period. Venetoclax will be continued at 400 mg QD from Week 6 (Day 1 of Cycle 1 of combination therapy) onwards up to disease progression (PD) or 2 years, whichever occurs first. R/C Substudy: venetoclax will be administered for 5-week dose ramp-up period to reach the target dose of 400 mg QD. Venetoclax will continue to be administered during the rituximab cycles until disease progression or for a maximum of 2 years from Cycle 1R/C Day 1 of the R/C Substudy.
- name
- Venetoclax
- other Names
- GDC-0199, ABT-199
- type
- DRUG
- arm Group Labels
- Bendamustine + Rituximab
- Bendamustine + Rituximab Crossover Substudy
- Venetoclax + Rituximab
- Venetoclax + Rituximab Re-Treatment
- description
- Rituximab will be administered at a dose of 375 mg/m\^2 via IV infusion on Day 1 of Cycle 1 and at a dose of 500 mg/m\^2 on Day 1 of Cycles 2-6. R/C Substudy: Following the venetoclax ramp-up period, rituximab will be administered for 6 cycles consisting of a single infusion on the first day of each 28-day cycle.
- name
- Rituximab
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 389
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- measure
- Change From Baseline in Lymphocyte Subset Counts at Specified Time Points
- time Frame
- Baseline, C4D14-28, Study Treatment Completion/Early Withdrawal (STC/EW, up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and at FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days
- primary Outcomes
- description
- 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 histology; decrease of \>/=50% compared to baseline in platelet or neutrophil count; or decrease in hemoglobin level by \>2 grams per deciliter (g/dL) or to less than \[\<\] 10 g/dL. Percentages are rounded off.
- measure
- Percentage of Participants With PD as Assessed by the Investigator Using Standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines or Death
- time Frame
- Baseline up to PD or death from any cause, whichever occurred first (up to approximately 8 years 5 months)
- description
- 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. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% confidence interval (CI) was computed using method of Brookmeyer and Crowley.
- measure
- Progression-Free Survival (PFS) as Assessed by the Investigator Using Standard iwCLL Guidelines
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
- secondary Outcomes
- description
- 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 hemoglobin level by \>2 g/dL or to \<10 g/dL. No new IRC data was generated post the primary analysis.
- measure
- Percentage of Participants With PD or Death as Assessed by the Independent Review Committee (IRC) Using Standard iwCLL Guidelines
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
- description
- 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. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley. No new IRC data was generated post the primary analysis.
- measure
- PFS as Assessed by the IRC Using Standard iwCLL Guidelines
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
- description
- 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 in hemoglobin level by \>2 g/dL or to \<10 g/dL. Percentages are rounded off.
- measure
- 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) Test
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
- description
- 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. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
- measure
- PFS as Assessed by the Investigator Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 8 years 5 months)
- description
- 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 hemoglobin level by \>2 g/dL or to \<10 g/dL. No new IRC data was generated post the primary analysis.
- measure
- 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 Test
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
- description
- 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. Participants who had not progressed, relapsed, or died at the time of analysis, were censored on the date of last assessment. In case of no disease assessment after baseline, PFS was censored at the time of randomization+1 day. The median PFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley. No new IRC data was generated post the primary analysis.
- measure
- PFS as Assessed by the IRC Using Standard iwCLL Guidelines in Participants With 17p Deletion as Identified by FISH Test
- time Frame
- Baseline up to PD or death, whichever occurred first (up to approximately 3 years)
- description
- 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 following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and 1 of following: neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL or \>/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. 95% CI was computed using Pearson-Clopper method.Percentages are rounded off.
- measure
- 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 Guidelines
- time Frame
- Baseline up to approximately 8 years 5 months
- description
- 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: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; 1 of following: neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL or \>/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. 95% CI was computed using Pearson-Clopper method.No new IRC data was generated post primary analysis.
- measure
- Percentage of Participants With Best Overall Response of CR, CRi, nPR, or PR as Assessed by the IRC Using iwCLL Guidelines
- time Frame
- Baseline up to last FUV (up to approximately 3 years)
- description
- 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 following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and 1 of following: neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL or \>/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. 95% CI was computed using Pearson-Clopper method. Percentages are rounded off.
- measure
- 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 Guidelines
- time Frame
- End of combination treatment response (EoCTR) visit (8 to 12 weeks after Cycle [C] 6 Day [1]); Cycle length = 28 days
- description
- 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 the following: peripheral blood lymphocytes, lymphadenopathy, spleen and/or liver enlargement; and one of the following: neutrophils \>1500/mcL, platelets \>100000/mcL, hemoglobin \>11.0 g/dL or \>/=50% improvement without need for transfusion or exogenous growth factors. nPR: fulfilling all CR criteria but presence of lymphoid nodules. The 95% CI was computed using Pearson-Clopper method.
- measure
- 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 Guidelines
- time Frame
- EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days
- description
- Percentage of participants who died from any cause, during the study, was reported. Percentage is rounded off.
- measure
- Percentage of Participants Who Died
- time Frame
- Baseline up to approximately 8 years 5 months
- description
- OS was defined as the time from the date of randomization to the date of death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. The median OS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.
- measure
- Overall Survival (OS)
- time Frame
- Baseline up to approximately 8 years 5 months
Full study description
- brief Summary
- 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).
Source references
- references
- citation
- Kater AP, Harrup R, Kipps TJ, Eichhorst B, Owen CJ, Assouline S, Lamanna N, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Mellink C, Langerak AW, Chyla B, Popovic R, Jiang Y, Millen R, Lefebure M, Thadani-Mulero M, Boyer M, Seymour JF. The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL. Blood. 2025 Jun 5;145(23):2733-2745. doi: 10.1182/blood.2024025525.
- pmid
- 40009494
- type
- DERIVED
- citation
- Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.
- pmid
- 35829925
- type
- DERIVED
- citation
- Seymour JF, Kipps TJ, Eichhorst BF, D'Rozario J, Owen CJ, Assouline S, Lamanna N, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Mellink C, Chyla B, Panchal A, Lu T, Wu JQ, Jiang Y, Lefebure M, Boyer M, Kater AP. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022 Aug 25;140(8):839-850. doi: 10.1182/blood.2021015014.
- pmid
- 35605176
- type
- DERIVED
- citation
- Kater AP, Wu JQ, Kipps T, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Robak T, de la Serna J, Jaeger U, Cartron G, Montillo M, Dubois J, Eldering E, Mellink C, Van Der Kevie-Kersemaekers AM, Kim SY, Chyla B, Punnoose E, Bolen CR, Assaf ZJ, Jiang Y, Wang J, Lefebure M, Boyer M, Humphrey K, Seymour JF. Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study. J Clin Oncol. 2020 Dec 1;38(34):4042-4054. doi: 10.1200/JCO.20.00948. Epub 2020 Sep 28.
- pmid
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- type
- DERIVED
- citation
- Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, Verdugo M, Wu J, Punnoose EA, Jiang Y, Wang J, Boyer M, Humphrey K, Mobasher M, Kipps TJ. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. J Clin Oncol. 2019 Feb 1;37(4):269-277. doi: 10.1200/JCO.18.01580. Epub 2018 Dec 3.
- pmid
- 30523712
- type
- DERIVED
- citation
- Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J, Jaeger U, Cartron G, Montillo M, Humerickhouse R, Punnoose EA, Li Y, Boyer M, Humphrey K, Mobasher M, Kater AP. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018 Mar 22;378(12):1107-1120. doi: 10.1056/NEJMoa1713976.
- pmid
- 29562156
- type
- DERIVED
- citation
- Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical Predictors of Venetoclax Pharmacokinetics in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patients: a Pooled Population Pharmacokinetic Analysis. AAPS J. 2016 Sep;18(5):1192-1202. doi: 10.1208/s12248-016-9927-9. Epub 2016 May 27.
- pmid
- 27233802
- type
- DERIVED
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Preserved source evidence · Not medical advice