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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04285567
Registration number
NCT04285567
Ethics application status
Date submitted
25/02/2020
Date registered
26/02/2020
Date last updated
17/04/2025
Titles & IDs
Public title
A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation
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Scientific title
A Prospective, Open-Label, Multicenter Randomized Phase III Study to Compare The Efficacy and Safety of A Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/Bendamustine and Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL(17P) or TP53 Mutation
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Secondary ID [1]
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2019-003327-37
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Secondary ID [2]
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CO41685
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Universal Trial Number (UTN)
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Trial acronym
CRISTALLO
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia (CLL)
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Venetoclax
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Rituximab
Treatment: Drugs - Bendamustine
Experimental: VEN + G - Participants will receive 12 cycles of treatment (each cycle is 28 days). Venetoclax (VEN) will be administered orally, daily, with a 5-week ramp-up period, starting on Cycle 1, Day 22 and administration will continue until the end of Cycle 12. Obinutuzumab (G) will be administered intravenously (IV) on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Active comparator: FCR/BR - Participants will receive 6 cycles of Fludarabine + Cyclophosphamide + Rituximab (FCR) consisting of a single cycle of a single infusion of rituximab on Day 1 and fludarabine and cyclophosphamide infusions on Days 1-3 of each 28-day cycle or bendamustine (B) as infusions on Days 1 and 2 and a single cycle of rituximab on Day 1 of each 28-day cycle.
Treatment: Drugs: Obinutuzumab
Obinutuzumab 1000 milligrams (mg) will be administered IV on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Treatment: Drugs: Venetoclax
Venetoclax 20 mg will be administered orally, once daily starting on Day 22 of Cycle 1 for 7 days, then ramp up from 50 to 400 mg/day during Cycle 2 and continue at 400 mg/day from Day 1 of Cycle 3 till end of Cycle 12.
Treatment: Drugs: Fludarabine
Fludarabine will be administered in a dosage of 25 milligram per meter squared (mg/m\^2), IV, on days 1, 2, and 3 of Cycles 1-6.
Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered in a dosage of 250 mg/m\^2, IV, on Days 1, 2, and 3 Cycles 1-6.
Treatment: Drugs: Rituximab
Rituximab will be administered at a dose of 375 mg/m\^2, IV, on Cycle 1, Day 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.
Treatment: Drugs: Bendamustine
Bendamustine will be administered at a dose of 90 mg/m\^2, IV, on 2 consecutive days of Cycles 1-6.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Minimal Residual Disease (MRD) Response Rate Measured in Peripheral Blood (PB) Using Next Generation Sequencing (NGS)
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Assessment method [1]
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MRD response rate was determined as the percentage of participants with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. Percentages have been rounded off to the nearest decimal point.
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Timepoint [1]
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At Month 15
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Secondary outcome [1]
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Progression-free Survival (PFS)
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Assessment method [1]
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PFS was defined as the time from randomization to the first occurrence of disease progression (PD), or death from any cause. PD was assessed by the investigators using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. PD was defined as any one of the following: Appearance of any new lesion such as enlarged lymph nodes (= 1.5 centimeters \[cm\]); increase by = 50% in greatest diameter of any previous site (= 1.5 cm); increase in the spleen/liver size by = 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/litres (L) B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of hemoglobin (Hb) = 2 grams per deciliter (g/dL) or 10 g/dL, or by a decrease of platelet counts = 50%/100x10\^9/L, which occurs at least 3 months after treatment.
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Timepoint [1]
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Up to approximately 74 months
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Secondary outcome [2]
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MRD Response Rate in PB of FCR/BR Compared With VEN+G at the End of Treatment Response Visit
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Assessment method [2]
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MRD response rate was determined as the percentage of participants with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. Percentages have been rounded off to the nearest decimal point.
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Timepoint [2]
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VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)
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Secondary outcome [3]
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MRD Response Rate in Bone Marrow (BM) of FCR/BR Compared With VEN+G at the End of Treatment Response Visit
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Assessment method [3]
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MRD response rate=percentage of participants with MRD-negativity measured in BM using NGS (cutoff of \<10\^-4). MRD negativity=\<1 CLL cell in 10,000 leukocytes. MRD in BM was assessed for participants with complete response (CR)/CR with incomplete blood count recovery (CRi) \& partial response (PR). CR=PB lymphocytes \<4x10\^9 /L; Absence of significant lymphadenopathy (nodes \<1.5 cm in longest diameter); no hepatomegaly/splenomegaly; absence of disease/constitutional symptoms; BM at least normocellular for age, =30% of nucleated cells being lymphocytes. CRi=fulfilling CR criteria but with persistent anemia/thrombocytopenia/neutropenia. PR= =50% decrease in PB lymphocyte count from pre-treatment value; =50% reduction in lymphadenopathy (sum of longest diameter of up to 6 largest lymph nodes by physical exam \& 50% reduction in the sum of product of the diameter of up to 6 largest lymph nodes); =50% reduction of liver/spleen enlargement/normalization in size, if enlarged at baseline.
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Timepoint [3]
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VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)
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Secondary outcome [4]
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Objective Response Rate (ORR)
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Assessment method [4]
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ORR was defined as the percentage of participants with overall response (OR) of CR, CRi, and PR as determined by the investigator according to the iwCLL guidelines. CR was defined as PB lymphocytes \<4x10\^9 /L; absence of significant lymphadenopathy (nodes \<1.5 cm in longest diameter \[LD\]); no hepatomegaly/splenomegaly; absence of disease/constitutional symptoms; BM at least normocellular for age, =30% of nucleated cells being lymphocytes. CRi was defined as fulfilling CR criteria but with persistent anemia/thrombocytopenia/neutropenia. PR was defined as =50% decrease in PB lymphocyte count from pre-treatment value; =50% reduction in lymphadenopathy sum of longest diameter of up to 6 largest lymph nodes by physical exam and 50% reduction in the sum of product of the diameter of up to 6 largest lymph nodes); =50% reduction of liver/spleen enlargement/normalization in size, if enlarged at baseline.
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Timepoint [4]
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At Month 15
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Secondary outcome [5]
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CR Rate
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Assessment method [5]
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CR rate was defined as the percentage of participants with CR or CRi. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes (evaluated by blood and differential count) below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, =30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.
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Timepoint [5]
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At Month 15
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Secondary outcome [6]
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MRD Response Rate in PB of Participants With a CR/CRi at the End of Treatment Visit
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Assessment method [6]
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MRD response rate was determined as the percentage of participants (with a CR/CRi) with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, =30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.
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Timepoint [6]
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At Month 15
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Secondary outcome [7]
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MRD Response Rate in BM of Participants With a CR/CRi at the End of Treatment Visit
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Assessment method [7]
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MRD response rate was determined as the percentage of participants (with CR/CRi) with MRD-negativity measured in the BM using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. CR/CRi were defined according to the iwCLL guidelines. CR was defined as one of the following: PB lymphocytes below 4 x 10\^9 /L; absence of significant lymphadenopathy (nodes \< 1.5 cm in LD or any extra nodal disease); no hepatomegaly; no splenomegaly; absence of disease or constitutional symptoms; BM at least normocellular for age, =30% of nucleated cells being lymphocytes. CRi was defined as participants fulfilling CR criteria with CR but had persistent anemia, thrombocytopenia, or neutropenia. Percentages have been rounded off to the nearest decimal point.
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Timepoint [7]
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VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)
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Secondary outcome [8]
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Duration of Objective Response (DOR)
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Assessment method [8]
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DOR was defined as the time from the first occurrence of a documented OR (CR, CRi and PR) to the time of PD as determined by the investigator, or death from any cause, whichever occurs first. CR, CRi, PR, and PD were defined according to the iwCLL guidelines. PD was defined as any one of the following: appearance of any new lesion such as enlarged lymph nodes (= 1.5 cm); increase by = 50% in greatest diameter of any previous site (= 1.5 cm); increase in the spleen/liver size by = 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb = 2 g/dL or 10 g/dL, or by a decrease of platelet counts = 50%/100x10\^9/L, which occurs at least 3 months after treatment. CR, CRi and PR were defined as outlined in the description for ORR outcome measure (OM) number 5.
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Timepoint [8]
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Up to approximately 74 months
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Secondary outcome [9]
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Best Overall Response (BOR)
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Assessment method [9]
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BOR=percentage of participants with CR/CRi/PR/stable disease (SD)/PD per the investigator. Participants with best response as CR/CRi/PR were considered responders while those reaching SD/PD were non-responders. SD=participants who have not achieved a CR or a PR, or who have not exhibited PD. PD=any one of the following: appearance of any new lesion such as enlarged lymph nodes (= 1.5 cm); increase by = 50% in greatest diameter of any previous site (= 1.5 cm); increase in the spleen/liver size by = 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb = 2 g/dL or 10 g/dL, or by a decrease of platelet counts = 50%/100x10\^9/L, which occurs at least 3 months after treatment. CR, CRi and PR were defined as outlined in the description for ORR, OM number 5.
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Timepoint [9]
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At Month 15
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Secondary outcome [10]
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Event-free Survival (EFS)
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Assessment method [10]
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EFS was defined as the time between the date of randomization and the date of PD/relapse, death, or the start of a new anti-leukemic therapy. PD was defined as any one of the following: appearance of any new lesion such as enlarged lymph nodes (= 1.5 cm); increase by = 50% in greatest diameter of any previous site (= 1.5 cm); increase in the spleen/liver size by = 50% or de novo appearance of splenomegaly/hepatomegaly; increase in blood lymphocytes by 50% or more with at least 5x10\^9/L B lymphocytes; transformation to a more aggressive histology; occurrence of cytopenia; posttreatment: progression of any cytopenia, documented by a decrease of Hb = 2 g/dL or 10 g/dL, or by a decrease of platelet counts = 50%/100x10\^9/L, which occurs at least 3 months after treatment.
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Timepoint [10]
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Up to approximately 74 months
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Secondary outcome [11]
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Overall Survival (OS)
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Assessment method [11]
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OS was defined as the time between the date of randomization and the date of death due to any cause.
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Timepoint [11]
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Up to approximately 74 months
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Secondary outcome [12]
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VEN + G: Tumor Lysis Syndrome (TLS) Risk Reduction Rate
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Assessment method [12]
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TLS risk reduction rate in the VEN + G arm was defined as the reduction in the percentage of participants who were TLS high-risk after 3 doses of obinutuzumab compared to the percentage of participants who were TLS high-risk at baseline. Risk for developing TLS were categorised into: Low - All measurable lymph nodes with the LD \< 5 cm and \< 25x10\^9/L absolute lymphocyte count (ALC); Medium - Any measurable lymph node with the LD =5 cm but \<10 cm OR =25x10\^9/L ALC; High - Any measurable lymph node with the LD =10 cm or the presence of both =25x10\^9/L ALC and any measurable lymph node with the LD =5 cm but \<10 cm. Percentages have been rounded off to the nearest decimal point.
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Timepoint [12]
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Baseline up to Cycle 1 Day 22 (1 cycle=28 days)
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Secondary outcome [13]
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VEN + G: Reduction in Mandatory Hospitalizations During Venetoclax Ramp-up
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Assessment method [13]
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Reduction in mandatory hospitalizations during venetoclax ramp-up in the VEN + G arm participants was defined as the actual number of protocol-mandated hospitalizations for TLS monitoring during venetoclax ramp-up period after 3 doses of obinutuzumab compared to the number of protocol-mandated hospitalizations for TLS monitoring during venetoclax ramp-up expected at baseline. Ramp-up period for venetoclax was defined as period from Cycle 1, Days 22-28, and Cycle 2, Day 1-Day 7 where the 20 mg and 50 mg daily doses of venetoclax, were administered for participants at TLS-high risk requiring mandated hospitalizations (the hospitalizations at 100, 200 and 400 was only needed if the participant had a TLS event at one of the lower doses). Total number of hospitalizations in high-risk TLS participants at baseline (expected to be N=2 hospitalization) was compared with the number of protocol mandated hospitalizations during the first 2 doses of the ramp-up.
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Timepoint [13]
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Cycle 1 Days 22-28 up to Cycle 2 Days 1-7 (1 cycle=28 days)
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Secondary outcome [14]
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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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Assessment method [14]
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An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that meets any of the following criteria: is fatal; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; is a significant medical event in the investigator's judgment.
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Timepoint [14]
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From Day 1 until 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy (up to 74 months)
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Secondary outcome [15]
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Number of Participants With Premature Withdrawals Due to AEs
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Assessment method [15]
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An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE was any AE that meets any of the following criteria: is fatal; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug; is a significant medical event in the investigator's judgment.
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Timepoint [15]
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From Day 1 until 28 days after the last dose of study drug, or until initiation of another anti-cancer therapy (up to 74 months)
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Secondary outcome [16]
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Change From Baseline in Physical Functioning, Role Functioning and Health-Related Quality of Life (HRQoL) Assessed Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQC-30)
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Assessment method [16]
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The EORTC QLQ-C30 consists 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 quality-of-life (GHS/QoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 28 function and symptom items were scored on a 4-point scale that ranged from "not at all" to "very much," and the 2 GHS/QoL items were scored on a 7-point scale that ranged from "very poor" to "excellent." Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e. higher functioning, higher symptom severity).
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Timepoint [16]
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VEN + G: Day 1 of Cycle 1-12, Day 28 after treatment completion/early termination (TC/ET), follow up (FU) visits; FCR/BR: Day 1 of Cycle 1-6, Day 28 after TC/ET, end of combination treatment response visit and FU visit (up to 74 months) (1 cycle=28 days)
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Secondary outcome [17]
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Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score
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Assessment method [17]
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MDASI-CLL consists of 25 items over 3 scales that assess core cancer \& CLL-related symptom severity, as well as symptom interference that a participant may have experienced in past 24 hours. Participants were asked to rate severity of 13 symptoms called mean core symptom severity (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting \& numbness/tingling), 6 disease-specific symptoms called mean module symptom severity (night sweats, fever \& chills, lymph node swelling, diarrhea, easy bruising/bleeding \& constipation) \& 6 mean interference on life questions (general activity, walking, work, mood, relations with other people \& enjoyment of life) on a scale from 0-10 with 0 indicating that symptom is "not present" or "did not interfere" with participant's activities \& 10 indicating "as bad as you can imagine" or "interfered completely". Lower scores indicated lower symptom severity/interference.
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Timepoint [17]
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VEN + G: Day 1 of Cycle 1-12, Day 28 after TC/ET, FU visits; FCR/BR: Day 1 of Cycle 1-6, Day 28 after TC/ET, end of combination treatment response visit and FU visit (up to approximately 74 months) (1 cycle=28 days)
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Eligibility
Key inclusion criteria
* Ability to comply with the study protocol, in the investigator's judgment
* Aged 18 years or older
* Have previously untreated documented Chronic Lymphocytic Leukemia (CLL) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
* CLL requiring treatment according to the iwCLL criteria
* Cumulative Illness Rating Scale (CIRS) score = 6 and creatinine clearance (CrCl) = 70 mL/min
* Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional bone marrow (BM) dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM):
* Absolute neutrophil count = 1.0 x 109/L, unless there is BM involvement
* Platelet count = 75 x 109/L and more than 7 days since last transfusion, or = 30 x 109/L if there is BM involvement
* Adequate liver function as indicated by a total bilirubin, aspartate aminotransferase, and Alanine transaminase = 2 times the institutional upper limit of normal (ULN) value, unless directly attributable to the participant's CLL
* Life expectancy >6 months
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL)
* Participants with Small Lymphocyclic Lymphoma (SLL) only
* Known central nervous system involvement
* Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
* Detected del(17p) or TP53 mutation (valid test within 6-months from screening is required for randomisation)
* An individual organ/system impairment score of 4 as assessed by the Cumulative Illness Rating Scale (CIRS) definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
* Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
* History of prior malignancy
* Participants with infections requiring IV treatment (Grade 3 or 4) within the last 8 weeks prior to enrollment
* Evidence of other clinically significant uncontrolled conditions including but not limited to active or uncontrolled systemic infection (e.g., viral, bacterial, or fungal)
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* Hypersensitivity to fludarabine, bendamustine, cyclophosphamide, rituximab, obinutuzumab, or venetoclax or to any of the excipients (e.g., trehalose)
* Pregnant women and nursing mothers
* Vaccination with a live vaccine = 28 days prior to randomization
* Prisoners or participants who are institutionalized by regulatory or court order or persons who are in dependence to the Sponsor or an investigator
* History of illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
* Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology)
* Positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
* Participants with known infection with HIV or Human T-Cell Leukemia Virus 1 (HTLV-1)
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
* Received any of the following agents within 28 days prior to the first dose of study treatment:
* Immunotherapy
* Radiotherapy
* Hormone therapy
* Any therapies intended for the treatment of lymphoma/leukemia whether approved or experimental
* Participants who have received the following agents:
* Strong and moderate CYP3A inhibitors/inducers within 7 days prior to the initiation of study treatment
* Steroid therapy for anti-neoplastic intent with the exception of inhaled steroids for asthma, topical steroids, or replacement/stress corticosteroids within 7 days prior to the first dose of study drug administration
* Consumed grapefruit, grapefruit products, Seville oranges(including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug and throughout venetoclax administration
* Inability to swallow a large number of tablets.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/05/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/07/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
166
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Recruitment in Australia
Recruitment state(s)
ACT,NSW,TAS,VIC
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Recruitment hospital [1]
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Canberra Hospital - Canberra
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Recruitment hospital [2]
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Liverpool Hospital - Liverpool
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Recruitment hospital [3]
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Port Macquarie - Mid North Coast Cancer Institute - Port Macquarie
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Recruitment hospital [4]
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Royal North Shore Hospital - St Leonards
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Recruitment hospital [5]
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Royal Hobart Hospital - Hobart
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Recruitment hospital [6]
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Monash Health;Haematology Research - Clayton
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Recruitment hospital [7]
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0
Peter MacCallum Cancer Centre;Clinical Haematology - Melbourne
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Recruitment hospital [8]
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Northern Hospital;Oncology and/or Hematology - Melbourne
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Recruitment postcode(s) [1]
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2605 - Canberra
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Recruitment postcode(s) [2]
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0
2170 - Liverpool
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Recruitment postcode(s) [3]
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2444 - Port Macquarie
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Recruitment postcode(s) [4]
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2065 - St Leonards
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Recruitment postcode(s) [5]
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7000 - Hobart
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Recruitment postcode(s) [6]
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3168 - Clayton
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Recruitment postcode(s) [7]
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3050 - Melbourne
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Recruitment postcode(s) [8]
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3076 - Melbourne
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Recruitment outside Australia
Country [1]
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Colorado
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France
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Aquitaine
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Indre-et-Loire
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Nord
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France
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France
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Caen
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France
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Le Mans
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France
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Poitiers
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Reims
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Italy
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Italy
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Lazio
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Italy
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Liguria
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Italy
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Lombardia
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Italy
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Piemonte
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Italy
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Italy
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Umbria
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Barcelona
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Navarra
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Madrid
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Murcia
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Spain
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Sevilla
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Spain
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Toledo
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Ethics approval
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Summary
Brief summary
This study will evaluate the efficacy and safety of venetoclax and obinutuzumab (VEN + G) compared with fludarabine + cyclophosphamide + rituximab or bendamustine + rituximab (FCR/BR) in FIT participants (FIT is defined by a cumulative illness rating scale \[CIRS\]/score of =6 and a normal creatinine clearance of =70 mL/min) with previously untreated CLL without DEL(17P) or TP53 mutation requiring treatment. Eligible participants will be randomly assigned in a 1:1 ratio to receive either VEN + G (Arm A) or FCR/BR (Arm B).
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Trial website
https://clinicaltrials.gov/study/NCT04285567
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Contacts
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Hoffmann-La Roche
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing).
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When will data be available (start and end dates)?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
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Other Details
Attachment
Study protocol
https://cdn.clinicaltrials.gov/large-docs/67/NCT04285567/Prot_000.pdf
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/67/NCT04285567/SAP_001.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT04285567
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