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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) (MURANO)

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ClinicalTrials.gov Identifier: NCT02005471
Recruitment Status : Active, not recruiting
First Posted : December 9, 2013
Results First Posted : October 1, 2018
Last Update Posted : October 1, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Bendamustine Drug: Venetoclax Drug: Rituximab Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 389 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Phase III, Open-Label, Randomized Study in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia to Evaluate the Benefit of Venetoclax (GDC-0199/ABT-199) Plus Rituximab Compared With Bendamustine Plus Rituximab
Actual Study Start Date : March 17, 2014
Actual Primary Completion Date : May 8, 2017
Estimated Study Completion Date : December 21, 2021


Arm Intervention/treatment
Active Comparator: Bendamustine + Rituximab
Participants will receive bendamustine 70 milligrams per meter squared (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.
Drug: Bendamustine
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.

Drug: Rituximab
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.

Experimental: Venetoclax + Rituximab
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.
Drug: Venetoclax
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.
Other Name: GDC-0199, ABT-199

Drug: Rituximab
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.




Primary Outcome Measures :
  1. 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 3 years) ]
    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.

  2. 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 3 years) ]
    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.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. 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 3 years) ]
    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.

  4. 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 3 years) ]
    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.

  5. 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) ]
    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.

  6. 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) ]
    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.

  7. 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 last follow-up visit (FUV) (maximum up to data cut-off date, overall approximately 3 years) ]
    Response was assessed by the investigator 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.

  8. 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 (maximum up to data cut-off date, overall approximately 3 years) ]
    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.

  9. 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 ]
    Response was assessed by the investigator 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.

  10. 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 ]
    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.

  11. Percentage of Participants Who Died [ Time Frame: Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years) ]
    Percentage of participants who died from any cause, during the study, was reported.

  12. Overall Survival (OS) [ Time Frame: Baseline up to last FUV (maximum up to Data Cut-off date, overall approximately 3 years) ]
    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.

  13. 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 [ Time Frame: Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years) ]
    Percentage of participants with PD/relapse, death from any cause, or start of a new non-protocol-specified anti-CLL therapy as assessed by the investigator, during the study, was reported. 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.

  14. Event-Free Survival (EFS) as Assessed by the Investigator Using iwCLL Guidelines [ Time Frame: Baseline up to PD/relapse, start of a new anti-CLL therapy, or death from any cause, whichever occurred first (maximum up to Data Cut-off date, overall approximately 3 years) ]
    EFS was defined as the time from date of randomization until the date of PD/relapse, start of a new non-protocol-specified anti-CLL therapy, or death from any cause, whichever occurred first, as assessed by the investigator. 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 without any of the specified event at the time of analysis were censored at the date of last adequate response assessment. In case of no post-baseline response assessment, participants were censored at the randomization date. The median EFS was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.

  15. 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 [ Time Frame: From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years) ]
    Percentage of participants with PD as assessed by the investigator according to the iwCLL guidelines or death from any cause during the study was reported. 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. CR, CRi, nPR, and PR have been defined in previous outcomes, and are not repeated here due to space constraint.

  16. Duration of Responses (DOR) as Assessed by the Investigator Using iwCLL Guidelines [ Time Frame: From time of achieving best overall response until PD or death from any cause, whichever occurred first (up to approximately 3 years) ]
    DOR was defined as the time from first occurrence of a documented response of CR, CRi, nPR, or PR until PD/relapse, as assessed by the investigator according to the iwCLL guidelines, or death from any cause. 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 without PD or death after response were censored at the last date of adequate response assessment. The median DOR was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley. CR, CRi, nPR, and PR have been defined in previous outcomes, and are not repeated here due to space constraint.

  17. Percentage of Participants With Start of New Anti-CLL Treatment or Death as Assessed by the Investigator [ Time Frame: Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years) ]
    Percentage of participants with start of new non-protocol-specified anti-CLL therapy, as assessed by the investigator, or death from any cause, during the study, was reported.

  18. Time to New Anti-CLL Treatment (TTNT) as Assessed by the Investigator [ Time Frame: Baseline up to start of new ani-CLL therapy or death, whichever occurred first (up to approximately 3 years) ]
    TTNT was defined as the time from randomization until start of new non-protocol-specified anti-CLL treatment or death from any cause. Participants without the event at the time of analysis were censored at the last visit date for this outcome measure analysis. The median TTNT was estimated using Kaplan-Meier method and the 95% CI was computed using method of Brookmeyer and Crowley.

  19. Percentage of Participants With Minimal Residual Disease (MRD) Negativity at the EoCTR Visit [ Time Frame: EoCTR visit (8 to 12 weeks after C6D1); Cycle length = 28 days ]
    MRD-negativity was defined as the presence of <1 malignant B-cell per 10000 normal B-cells in a sample of at least 200000 B-cells, as assessed by the allele specific oligonucleotide polymerase chain reaction (ASO-PCR) and/or flow cytometry technique. Percentage of participants with MRD-negativity at the EoCTR visit was reported. The 95% CI was computed using Pearson-Clopper method.

  20. Plasma Venetoclax Concentrations [ Time Frame: Pre-dose (0 hour, anytime before venetoclax administeration) and 4 hours post-dose on D1 of Cycles 1 and 4; Cycle length = 28 days ]
  21. 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 ]
  22. Change From Baseline in Monroe Dunaway (MD) Anderson Symptom Inventory (MDASI) Core Symptom Severity, Module Symptom Severity, and Interference Scores [ Time Frame: Baseline, Days 1, 8, and 15 of Cycles 1, 2, and 3; Cycle length = 28 days ]
    MDASI is a 25-item validated questionnaire consisting of 2 parts. Part 1: 19-items divided into 2 scales, Core Symptom Severity (average of Questions 1 to 13; total 13 items: pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness) and Module Symptom Severity (average of Questions 14 to 19; total 6 items: night sweats, fevers and chills, lymph node swelling, diarrhea, bruising easy or bleeding, and constipation). Part 2: 6-items to assess Interference (symptom distress) (average of Questions 20 to 25; total 6 items: general activity, walking, work, mood, relations with other people, and enjoyment of life). Each item was rated from 0 to 10, with lower scores indicating better outcome. Total score for Core Symptom Severity, Module Symptom Severity, and Interference are reported which range from 0 to 10, with lower scores indicating better health-related quality of life (HRQoL).

  23. 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 [ Time Frame: Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days ]
    The EORTC QLQ-C30 is a validated self-report measure consisting of 30 questions incorporated into five functional scales (Physical, Role, Cognitive, Emotional, and Social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), a global health status/global QoL scale, and single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea). Most questions used 4-point scale (1='Not at all' to 4='Very much'), while 2 questions used 7-point scale (1='very poor' to 7='Excellent'). Functional scales score and global health status/global QoL scale score are reported. Scores were averaged, transformed to 0-100 scale; where higher score for functional scales = poor level of functioning and higher score for global health status/global QoL = better HRQoL.

  24. Change From Baseline in HRQoL as Measured by Quality of Life Questionnaire Associated CLL Module (QLQ-CLL16) Multi-Item Scales Score [ Time Frame: Baseline, D1 of Cycles 1, 2, 3, 4, 5, 6, STC/EW visit (up to C6D28), EoCTR visit (8 to 12 weeks after C6D1), and FUVs (every 12 weeks after EoCTR up to 3 years); Cycle length = 28 days ]
    The EORTC QLQ-CLL16 module is designed for participants with Stage 0 to Stage 4 CLL. It is composed of 16 questions and there are four multi-item scales on Fatigue (2 items), Treatment-related side effects (TRSE, 4 items), Disease-related symptoms (DRS, 4 items), and Infection (4 items); and two single-item scales on social activities and future health worries. Multi-item scales score are reported and the total score for each multi-item scale was transformed to result in a total score range of 0 to 100, where higher score = poor HRQoL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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

Information from the National Library of Medicine

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): NCT02005471


  Show 163 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
AbbVie
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] November 21, 2016
Statistical Analysis Plan  [PDF] May 18, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02005471     History of Changes
Other Study ID Numbers: GO28667
2013-002110-12 ( EudraCT Number )
First Posted: December 9, 2013    Key Record Dates
Results First Posted: October 1, 2018
Last Update Posted: October 1, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Venetoclax
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action