Clinical trial NCT02966756: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-11-17
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Measured up to 2 years after the last participant has enrolled in the study.
Secondary outcomes:
measure: Complete Response Rate (CRR)
timeFrame: Measured up to 2 years after the last participant has enrolled into the study.
measure: Duration of Overall Response (DOR)
timeFrame: Measured up to 2 years after the last participant has enrolled into the study.
measure: Progression Free Survival (PFS)
timeFrame: Measured up to 5 years after the last participant has enrolled into the study.
measure: Event Free Survival (EFS)
timeFrame: Measured up to 5 years after the last participant has enrolled into the study.
measure: Time to Progression (TTP)
timeFrame: Measured up to 5 years after the last participant has enrolled into the study.
measure: Time to 50% reduction in absolute lymphocyte count (ALC)
timeFrame: Measured up to 2 years after the last participant has enrolled into the study.
measure: Overall Survival (OS)
timeFrame: Measured up to 5 years after the last participant has enrolled into the study.
Other outcomes:
Locations:
city: Concord
country: Australia
facility: Concord Repatriation General Hospital /ID# 201261
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital /ID# 206484
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 201263
state: Victoria
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital /ID# 209458
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital /ID# 156575
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital (East) - Dongdan Campus /ID# 156576
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital /ID# 156579
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital /ID# 160509
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University /ID# 156571
state: Guangdong
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University /ID# 159143
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital /ID# 156573
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST /ID# 156589
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University /ID# 208913
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital /ID# 156577
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University /ID# 156536
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University /ID# 159142
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University /ID# 156532
state: Jilin
city: Jinan
country: China
facility: Shandong Provincial Hospital /ID# 156574
state: Shandong
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University /ID# 156537
state: Sichuan
city: Chengdu
country: China
facility: The General Hospital of Western Theater Command PLA /ID# 159145
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 157762
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital /ID# 156542
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578
state: Zhejiang
city: Takapuna
country: New Zealand
facility: North Shore Hospital /ID# 204637
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital /ID# 201650
state: Canterbury
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 210733
state: Taipei
city: Changhua City, Changhua County
country: Taiwan
facility: Changhua Christian Hospital /ID# 202768
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 202767
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 203636
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: