A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Conditions
- Chronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)
- Interventions
- Registration Number
- NCT02966756
- Lead Sponsor
- AbbVie
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 110
-
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.
-
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 or other BCL-2 inhibitors.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Venetoclax Venetoclax Participants with 17p deletion status will receive various doses of venetoclax once daily (QD). Cohort 2: Venetoclax Venetoclax 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).
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Measured up to 2 years after the last participant has enrolled in the study. 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
Name Time Method Time to 50% reduction in absolute lymphocyte count (ALC) Measured up to 2 years after the last participant has enrolled into the study. 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.
Complete Response Rate (CRR) Measured up to 2 years after the last participant has enrolled into the study. 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) Measured up to 2 years after the last participant has enrolled into the study. 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) Measured up to 5 years after the last participant has enrolled into the study. 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) Measured up to 5 years after the last participant has enrolled into the study. 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) Measured up to 5 years after the last participant has enrolled into the study. 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).
Overall Survival (OS) Measured up to 5 years after the last participant has enrolled into the study. OS is defined as number of days from the date of first dose to the date of death.
Trial Locations
- Locations (31)
Monash Health - Monash Medical Centre /ID# 201263
🇦🇺Clayton, Victoria, Australia
Peking Union Medical College Hospital (East) - Dongdan Campus /ID# 156576
🇨🇳Beijing, Beijing, China
Concord Repatriation General Hospital /ID# 201261
🇦🇺Concord, New South Wales, Australia
St George Hospital /ID# 206484
🇦🇺Kogarah, New South Wales, Australia
Anhui Provincial Cancer Hospital /ID# 209458
🇨🇳Hefei, Anhui, China
Peking University People's Hospital /ID# 156575
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital /ID# 156579
🇨🇳Fuzhou, Fujian, China
Guangdong Provincial People's Hospital /ID# 160509
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University /ID# 156571
🇨🇳Guangzhou, Guangdong, China
The Second Hospital of Hebei Medical University /ID# 159143
🇨🇳Shijiazhuang, Hebei, China
Henan Cancer Hospital /ID# 156573
🇨🇳Zhengzhou, Henan, China
Tongji Hospital Tongji Medical College of HUST /ID# 156589
🇨🇳Wuhan, Hubei, China
Xiangya Hospital Central South University /ID# 208913
🇨🇳Changsha, Hunan, China
Jiangsu Province Hospital /ID# 156577
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University /ID# 156536
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University /ID# 159142
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University /ID# 156532
🇨🇳Changchun, Jilin, China
Shandong Provincial Hospital /ID# 156574
🇨🇳Jinan, Shandong, China
Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University /ID# 156537
🇨🇳Chengdu, Sichuan, China
The General Hospital of Western Theater Command PLA /ID# 159145
🇨🇳Chengdu, Sichuan, China
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 157762
🇨🇳Tianjin, Tianjin, China
Tianjin Medical University Cancer Institute & Hospital /ID# 156542
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578
🇨🇳Hangzhou, Zhejiang, China
North Shore Hospital /ID# 204637
🇳🇿Takapuna, Auckland, New Zealand
Christchurch Hospital /ID# 201650
🇳🇿Christchurch, Canterbury, New Zealand
National Taiwan University Hospital /ID# 210733
🇨🇳Taipei City, Taipei, Taiwan
Changhua Christian Hospital /ID# 202768
🇨🇳Changhua City, Changhua County, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital /ID# 202767
🇨🇳Taichung, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 203636
🇨🇳Taoyuan City, Taiwan