Back to resultsA Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Primary Purpose
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring Relapsed chronic lymphocytic leukemia (CLL), Refractory chronic lymphocytic leukemia (CLL), 17p deletion, Venetoclax, Leukemia, Lymphoproliferative Disorders, Small Lymphocytic Lymphoma (SLL), Venclexta
Eligibility Criteria
Inclusion Criteria:
Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines and the following:
- Participant must have an indication for treatment according to the 2008 Modified iwCLL NCI-WG Guidelines.
- SLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10^9/L or an enlarged lymph node(s) (Longest Diameter (LDi) > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL).
- SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate.
- Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy.
- Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory.
Participants (in Cohort 2) must meet both of the following:
- Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment;
- And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having known 17p deletion or TP53 mutation, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine clearance <70 mL/min.
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
- Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening.
- No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Exclusion Criteria:
- Participant has undergone an allogeneic stem cell transplant.
- Participant has developed Richter's transformation confirmed by biopsy.
- Participant has prolymphocytic leukemia.
- Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
- Participant has previously received venetoclax.
- Participant is known to be positive for Human Immunodeficiency Virus (HIV).
- Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents.
- Investigational therapy, including targeted small molecule agents.
- Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.
Sites / Locations
- Concord Repatriation General Hospital /ID# 201261Recruiting
- St George Hospital /ID# 206484Recruiting
- Monash Medical Centre /ID# 201263Recruiting
- Anhui Provincial Cancer Hospital /ID# 209458Recruiting
- Peking University People's Hospital /ID# 156575Recruiting
- Peking Union Medical College Hospital /ID# 156576Recruiting
- Fujian Medical University Union Hospital /ID# 156579Recruiting
- Guangdong Provincial People's Hospital /ID# 160509Recruiting
- Nanfang Hospital of Southern Medical University /ID# 156571Recruiting
- The Second Hospital of Hebei Medical University /ID# 159143
- Henan Cancer Hospital /ID# 156573Recruiting
- Tongji Hospital Tongji Medical College of HUST /ID# 156589Recruiting
- Xiangya Hospital Central South University /ID# 208913Recruiting
- Jiangsu Province Hospital /ID# 156577Recruiting
- The First Affiliated Hospital of Soochow University /ID# 156536Recruiting
- The First Affiliated Hospital of Nanchang University /ID# 159142Recruiting
- The First Hospital of Jilin University /ID# 156532Recruiting
- Shandong Provincial Hospital /ID# 156574Recruiting
- Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572Recruiting
- West China Hospital, Sichuan University /ID# 156537Recruiting
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 157762Recruiting
- Tianjin Medical University Cancer Institute & Hospital /ID# 156542Recruiting
- The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578Recruiting
- The General Hospital of Western Theater Command PLA /ID# 159145Recruiting
- North Shore Hospital /ID# 204637Recruiting
- Christchurch Hospital /ID# 201650Recruiting
- Changhua Christian Hospital /ID# 202768
- Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765Recruiting
- China Medical University Hospital /ID# 202767Recruiting
- National Taiwan University Hospital /ID# 210733Recruiting
- Linkou Chang Gung Memorial Hospital /ID# 203636Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: Venetoclax
Cohort 2: Venetoclax
Arm Description
Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).
Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD).
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR)
ORR is the proportion of participants with an overall response (complete remission [CR], plus complete remission with incomplete bone marrow recovery [CRi], plus nodular partial remission [nPR], plus partial remission [PR]) per the National Cancer Institute-Working Group (NCI-WG) guidelines as assessed by the Independent Review Committee (IRC).
Secondary Outcome Measures
Complete Response Rate (CRR)
CRR is defined as the proportion of subjects who achieved (CR + CRi) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) NCI-WG criteria.
Duration of Overall Response (DOR)
DOR is defined as the number of days from the date of first (CR + CRi + nPR + PR) to the earliest disease progression or death
Progression Free Survival (PFS)
PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC) or death.
Event Free Survival (EFS)
EFS is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.
Time to Progression (TTP)
TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC).
Time to 50% reduction in absolute lymphocyte count (ALC)
Time to 50% reduction in ALC is defined as the number of days from the date of first dose to the date when the ALC has reduced to 50% of the baseline value.
Overall Survival (OS)
OS is defined as number of days from the date of first dose to the date of death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02966756
Brief Title
A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Official Title
A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 12, 2017 (Actual)
Primary Completion Date
May 30, 2029 (Anticipated)
Study Completion Date
May 30, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, open-label, multicenter study, evaluating the efficacy of venetoclax in participants with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) either in presence of 17p deletion (Cohort 1) or those who have failed a B-receptor signaling pathway inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status (Cohort 2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Keywords
Relapsed chronic lymphocytic leukemia (CLL), Refractory chronic lymphocytic leukemia (CLL), 17p deletion, Venetoclax, Leukemia, Lymphoproliferative Disorders, Small Lymphocytic Lymphoma (SLL), Venclexta
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
110 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Venetoclax
Arm Type
Experimental
Arm Description
Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).
Arm Title
Cohort 2: Venetoclax
Arm Type
Experimental
Arm Description
Participants who have failed a B-Cell Receptor Signaling Pathway Inhibitor (BCRI) therapy and who have also failed, or were unable to receive chemoimmunotherapy (CIT) irrespective of 17p status will receive various doses of venetoclax once daily (QD).
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199, GDC-0199, Venclexta
Intervention Description
Tablet; Oral
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is the proportion of participants with an overall response (complete remission [CR], plus complete remission with incomplete bone marrow recovery [CRi], plus nodular partial remission [nPR], plus partial remission [PR]) per the National Cancer Institute-Working Group (NCI-WG) guidelines as assessed by the Independent Review Committee (IRC).
Time Frame
Measured up to 2 years after the last participant has enrolled in the study.
Secondary Outcome Measure Information:
Title
Complete Response Rate (CRR)
Description
CRR is defined as the proportion of subjects who achieved (CR + CRi) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) NCI-WG criteria.
Time Frame
Measured up to 2 years after the last participant has enrolled into the study.
Title
Duration of Overall Response (DOR)
Description
DOR is defined as the number of days from the date of first (CR + CRi + nPR + PR) to the earliest disease progression or death
Time Frame
Measured up to 2 years after the last participant has enrolled into the study.
Title
Progression Free Survival (PFS)
Description
PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC) or death.
Time Frame
Measured up to 5 years after the last participant has enrolled into the study.
Title
Event Free Survival (EFS)
Description
EFS is defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy.
Time Frame
Measured up to 5 years after the last participant has enrolled into the study.
Title
Time to Progression (TTP)
Description
TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (determined by the IRC).
Time Frame
Measured up to 5 years after the last participant has enrolled into the study.
Title
Time to 50% reduction in absolute lymphocyte count (ALC)
Description
Time to 50% reduction in ALC is defined as the number of days from the date of first dose to the date when the ALC has reduced to 50% of the baseline value.
Time Frame
Measured up to 2 years after the last participant has enrolled into the study.
Title
Overall Survival (OS)
Description
OS is defined as number of days from the date of first dose to the date of death.
Time Frame
Measured up to 5 years after the last participant has enrolled into the study.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must have a diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) that meets 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (iwCLL) National Cancer Institute-Working Group (NCI-WG) Guidelines and the following:
Participant must have an indication for treatment according to the 2008 Modified iwCLL NCI-WG Guidelines.
SLL participant must have measurable disease (B-lymphocytosis greater than 5 × 10^9/L or an enlarged lymph node(s) (Longest Diameter (LDi) > 1.5 cm at baseline) or hepatomegaly or splenomegaly due to CLL).
SLL participant must have presence of lymphadenopathy and absence of cytopenias caused by a clonal marrow infiltrate.
Participant must have relapsed or refractory CLL/SLL after receiving at least one prior line of therapy.
Participants (in Cohort 1) must have 17p deletion, assessed by a central laboratory.
Participants (in Cohort 2) must meet both of the following:
Relapsed/refractory disease to B-Cell Receptor Signaling Pathway Inhibitor (BCRI) treatment;
And either of the following: (a) relapsed/refractory disease to chemoimmunotherapy (CIT), or (b) ineligible to receive CIT, defined as having known 17p deletion or TP53 mutation, or Cumulative Illness Rating Scale (CIRS) >6 or calculated creatinine clearance <70 mL/min, or participants in whom the investigator evaluated that the use of CIT was inappropriate.
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening.
No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Exclusion Criteria:
Participant has undergone an allogeneic stem cell transplant.
Participant has developed Richter's transformation confirmed by biopsy.
Participant has prolymphocytic leukemia.
Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP).
Participant has previously received venetoclax.
Participant is known to be positive for Human Immunodeficiency Virus (HIV).
Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
Participant has received any of the following within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of venetoclax, or has not recovered to less than Common Toxicity Criteria for Adverse Events (CTCAE) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
Any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy or targeted small molecule agents.
Investigational therapy, including targeted small molecule agents.
Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ABBVIE CALL CENTER
Phone
844-663-3742
Email
abbvieclinicaltrials@abbvie.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Concord Repatriation General Hospital /ID# 201261
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Individual Site Status
Recruiting
Facility Name
St George Hospital /ID# 206484
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Name
Monash Medical Centre /ID# 201263
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
Anhui Provincial Cancer Hospital /ID# 209458
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230031
Country
China
Individual Site Status
Recruiting
Facility Name
Peking University People's Hospital /ID# 156575
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Name
Peking Union Medical College Hospital /ID# 156576
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Name
Fujian Medical University Union Hospital /ID# 156579
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Individual Site Status
Recruiting
Facility Name
Guangdong Provincial People's Hospital /ID# 160509
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Name
Nanfang Hospital of Southern Medical University /ID# 156571
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Recruiting
Facility Name
The Second Hospital of Hebei Medical University /ID# 159143
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Individual Site Status
Completed
Facility Name
Henan Cancer Hospital /ID# 156573
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Individual Site Status
Recruiting
Facility Name
Tongji Hospital Tongji Medical College of HUST /ID# 156589
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Individual Site Status
Recruiting
Facility Name
Xiangya Hospital Central South University /ID# 208913
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410008
Country
China
Individual Site Status
Recruiting
Facility Name
Jiangsu Province Hospital /ID# 156577
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Soochow University /ID# 156536
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital of Nanchang University /ID# 159142
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Individual Site Status
Recruiting
Facility Name
The First Hospital of Jilin University /ID# 156532
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130021
Country
China
Individual Site Status
Recruiting
Facility Name
Shandong Provincial Hospital /ID# 156574
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250021
Country
China
Individual Site Status
Recruiting
Facility Name
Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200065
Country
China
Individual Site Status
Recruiting
Facility Name
West China Hospital, Sichuan University /ID# 156537
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Individual Site Status
Recruiting
Facility Name
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 157762
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Name
Tianjin Medical University Cancer Institute & Hospital /ID# 156542
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300060
Country
China
Individual Site Status
Recruiting
Facility Name
The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310006
Country
China
Individual Site Status
Recruiting
Facility Name
The General Hospital of Western Theater Command PLA /ID# 159145
City
Chengdu
ZIP/Postal Code
610083
Country
China
Individual Site Status
Recruiting
Facility Name
North Shore Hospital /ID# 204637
City
Takapuna
State/Province
Auckland
ZIP/Postal Code
0622
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Christchurch Hospital /ID# 201650
City
Christchurch
State/Province
Canterbury
ZIP/Postal Code
8011
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Changhua Christian Hospital /ID# 202768
City
Changhua City, Changhua County
ZIP/Postal Code
50006
Country
Taiwan
Individual Site Status
Completed
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
China Medical University Hospital /ID# 202767
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
National Taiwan University Hospital /ID# 210733
City
Taipei City
ZIP/Postal Code
100
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Linkou Chang Gung Memorial Hospital /ID# 203636
City
Taoyuan City
ZIP/Postal Code
333
Country
Taiwan
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
IPD Sharing Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
IPD Sharing Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
IPD Sharing URL
https://vivli.org/ourmember/abbvie/
Links:
URL
https://www.abbvieclinicaltrials.com/study/?id=M14-728
Description
Related Info
Learn more about this trial
A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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