Clinical Trial Results:
Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Impact of Venetoclax on the Quality of Life of Relapsed/Refractory Subjects with Chronic Lymphocytic Leukemia (CLL) (VENICE II)
Summary
|
|
EudraCT number |
2016-001097-15 |
Trial protocol |
HU PL BG |
Global end of trial date |
29 Dec 2021
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
12 Mar 2023
|
First version publication date |
06 Jan 2023
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
M15-889
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02980731 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
|
||
Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road,, Maidenhead, Berkshire, United Kingdom, SL6 4UB
|
||
Public contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
|
||
Scientific contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
29 Dec 2021
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Dec 2021
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The purpose of this open-label, single-arm study was to evaluate the impact of venetoclax on the quality of life of participants including those with with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL; a type of cancer affecting the blood and the bone marrow) with or without the 17p deletion or TP53 mutation, including participants with an unknown status, as well as R/R CLL participants who had been previously treated with B-cell receptor inhibitor (BCRi) therapy. The starting dose of venetoclax was 20 mg once daily. The dose must have been gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Participants may have continued receiving venetoclax for up to 2 years. After the treatment period, participants may have continued on into a 2-year follow-up period.
|
||
Protection of trial subjects |
The Investigator or his/her representative explained the nature of the study to the subject and answered all questions regarding this study. Prior to any study-related screening procedure being performed on the subject the informed consent statement was reviewed, signed and dated by the subject, the person who administered the informed consent, and any other signatories according to local requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Dec 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Argentina: 4
|
||
Country: Number of subjects enrolled |
Australia: 57
|
||
Country: Number of subjects enrolled |
Bulgaria: 14
|
||
Country: Number of subjects enrolled |
Hong Kong: 1
|
||
Country: Number of subjects enrolled |
Hungary: 16
|
||
Country: Number of subjects enrolled |
Mexico: 11
|
||
Country: Number of subjects enrolled |
New Zealand: 23
|
||
Country: Number of subjects enrolled |
Poland: 22
|
||
Country: Number of subjects enrolled |
Russian Federation: 46
|
||
Country: Number of subjects enrolled |
Taiwan: 16
|
||
Worldwide total number of subjects |
210
|
||
EEA total number of subjects |
52
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
102
|
||
From 65 to 84 years |
107
|
||
85 years and over |
1
|
|
|||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||
Screening details |
Participants underwent screening procedures within 28 days prior to initial venetoclax administration, with the exception of the CT scan (or MRI if CT was medically contraindicated). A CT scan was accepted if previously performed within 35 days prior to venetoclax administration. | ||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||
Arm title
|
Venetoclax | ||||||||||||||||||||||
Arm description |
Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Venetoclax
|
||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||
Other name |
ABT-199, VENCLEXTA, VENCLYXTO
|
||||||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||
Dosage and administration details |
Venetoclax tablets were to be taken orally once daily with a meal and water in the morning at approximately the same time each day. Tablets were to be swallowed whole and not chewed, crushed, or broken prior to swallowing.
|
||||||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Venetoclax
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Venetoclax
|
||
Reporting group description |
Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 weeks. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. |
|
|||||||||
End point title |
Mean Change from Baseline to Week 48 in Global Health Status/Quality of Life (GHS/QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) [1] | ||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline, Week 48
|
||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: A paired t-test of H0: mean difference (Week 48 - baseline) ≤5 versus H1: mean difference (Week 48 - baseline) > 5 was conducted, with p=0.004. |
|||||||||
|
|||||||||
Notes [2] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the global health status/quality of life scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [3] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Physical Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [4] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Role Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [5] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Emotional Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an emotional functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the emotional functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [6] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Cognitive Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a cognitive functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the cognitive functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [7] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Social Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a social functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social functioning scale indicates a better level of functioning, and positive changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [8] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change from Baseline in Fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a fatigue scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [9] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Nausea and Vomiting Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a nausea and vomiting scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the nausea and vomiting scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [10] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Pain Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a pain scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the pain scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [11] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Dyspnea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a dyspnea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the dyspnea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [12] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Insomnia Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an insomnia scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the insomnia scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [13] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Appetite Loss Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including an appetite loss scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the appetite loss scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [14] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Constipation Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a constipation scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the constipation scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [15] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Diarrhea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a diarrhea scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the diarrhea scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [16] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Financial Difficulties Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a financial difficulties scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the financial difficulties scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [17] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the fatigue scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [18] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Treatment Side Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the treatment side effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [19] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Disease Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the disease effects scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [20] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Infection Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the infection scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [21] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Social Problems Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the social problems scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [22] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in Future Health Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16) | ||||||||||||||||||||||||||||||||
End point description |
EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life important in CLL. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the future health scale indicates a lower level of functioning, and negative changes from baseline indicate improvement. A change of 5 – 10 points is considered a small change, and a change of 10 – 20 points is considered a moderate change.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [23] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale Score | ||||||||||||||||||||||||||||||||
End point description |
The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). Participants rated their health on a vertical visual analogue scale, where the endpoints were labelled 100, "The best health you can imagine" and 0, "The worst health you can imagine". Positive values indicate improvement from baseline.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [24] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Index Score | ||||||||||||||||||||||||||||||||
End point description |
The EQ-5D 5L measures quality of life in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on five levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems), and a separate visual analog scale (VAS). The scores for the 5 dimensions are used to compute a single utility index score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual, with '0' defined as a health state equivalent to being dead and '1' is full health. The higher
the score the better the health status. Positive values indicate improvement from baseline.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [25] - All enrolled subjects who received at least one dose of venetoclax with available data |
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Complete Remission Rate (Complete Remission [CR] + Complete Remission With Incomplete Marrow Recovery [CRi]) | ||||||||
End point description |
Complete remission rate (CR + CRi) is defined as the percentage of participants achieving a CR or CRi as their best response (per the investigator assessment) based on 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [26] - All enrolled participants who received at least one dose of venetoclax |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall Response Rate (ORR) | ||||||||
End point description |
ORR is defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines criteria as assessed by investigator using the best response at any time during the study.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [27] - Subjects who rcvd ≥ 1 dose of venetoclax; those who didn’t respond were considered non-responders |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Duration of Overall Response (DOR) | ||||||||
End point description |
DoR is defined as the number of days from the date of first response (complete remission (CR), complete remission with incomplete marrow recovery (CRi), nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute Working Group (NCI-WG) Guidelines criteria to the earliest date of progressive disease (PD) or death. DOR was analyzed by Kaplan-Meier (K-M) methodology.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [28] - Subjects rcvd ≥ 1 dose venetoclax, active disease at baseline, achieved response of PR or better |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Time to Progression (TTP) | ||||||||
End point description |
TTP is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD). TTP was analyzed by Kaplan-Meier (K-M) methodology.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [29] - All enrolled participants who received at least one dose of venetoclax |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Progression-Free Survival (PFS) | ||||||||
End point description |
PFS is defined as the number of days from the date of first dose of venetoclax to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [30] - All enrolled participants who received at least one dose of venetoclax |
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Overall Survival (OS) | ||||||||
End point description |
OS is defined as the number of days from the date of first dose of venetoclax to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology. In the table below, -999 and 99999 mean not calculable/estimable due to low number of participants with events.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
|
||||||||
|
|||||||||
Notes [31] - All enrolled participants who received at least one dose of venetoclax |
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All-cause mortality is reported from from enrollment to end of study; median time on follow up = 184 wks. TEAEs and SAEs were collected from first dose of study drug until 30 d after last dose of study drug; mean on study drug = 123 wks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Venetoclax
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Venetoclax was administered orally once daily (QD) for a planned duration of up to 2 years or until disease progression; median time on treatment was 127 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
11 Jul 2016 |
Amendment 1
● Modified text as it related to patients previously treated with a B-cell receptor inhibitor
● Clarified Exclusion Criteria, Criterion 11 regarding a subject’s known history of HIV status
● Allowed urine pregnancy testing at the Investigator's discretion
● Removed requirement of subject diaries throughout the protocol
|
||
30 Jan 2018 |
Amendment 2
● Updated number of planned study sites
● Clarified that relapsed/refractory subjects with or without the 17p deletion or TP53 mutation, including subjects with an unknown status, can be enrolled in the study, as well as subjects previously treated with B-cell receptor inhibitor therapy
● Clarified all screening procedures must be done in the screening period of 28 days, except a CT scan, which can be performed within 35 days of study drug administration
● Clarified that study visits occur within 72 hours of dosing and on the first and second day of Week 1 and 2 of the dose titration phase, for all subjects. Additionally, clarification was added beginning on Week 3 through Week 5, study visits will be conducted within 72 hours of dosing and on Day 1 of each week. Additional study visits on Day 2 of each week should be performed for subjects who continue to be at risk of TLS, based on investigator assessment.
● Implemented a Data Monitoring Committee (DMC) to review safety data
● Clarified that MRI will be accepted in the case when CT scan with contrast is medically contraindicated
● Included a 30-day safety follow up visit after the last dose of venetoclax to allow for continued AE collection
● Clarified that plasma values may be used in place of serum values for estimated creatinine clearance calculations depending on local laboratory standard testing requirements
● Clarified the treatment period for all subjects is 2 years
● Updated text to align with the current approach to TLS prophylaxis and management
● Clarified that the maximum dose of venetoclax administered for this protocol is 400 mg
● Clarified that overall survival is an efficacy endpoint
● Clarified timing of pre-and post-dose hematology/chemistry requirements and which labs are drawn and when for managing TLS
● Specified that immunizations with live virus vaccines should not be administered prior to, during, or after treatment with venetoclax until B-cell recovery occurs
|
||
09 Oct 2018 |
Amendment 3
● Updated Venetoclax Clinical Data section to align with the most recent version of the Investigator's Brochure.
● Added a ± 2 day visit window as of Week 8
● Clarified that Bone Marrow samples will be collected for subjects with Complete Response to confirm response
● Added that in countries where venetoclax is commercially available extension of therapy may not be allowed
● Removed requirement to evaluate lymph nodes at physical examinations at visits other than Screening and Weeks 24, 36 and 48
● Clarified that if the CT is negative a bone marrow biopsy will be obtained to confirm clinical response. If a CT scan is performed and does not confirm a clinical response, a bone marrow biopsy should not be obtained
● Added that for subjects with only Partial Remission at Week 48, an additional CT and a bone marrow examination can be done between Week 48 and Week 108 to confirm Complete Response if there is a possibility that a subject is in Complete Remission based on laboratory tests and a disease assessment physical examination
● Clarified that subjects will be followed for survival information every 6 months even if subjects had an event of progression, they require alternate therapy, etc.
● Added a window (± 7 days) to the post-treatment calls
● Added that Adverse Event/Concomitant medication assessment is to be done also at the following visits: within 72 hours of W2 D1, W3 D1, W4 D1 and W5 D1
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |