A Study of Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02966756
• Other study ID #: M14-728
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2017
• Est. completion date: May 30, 2029

Study information

• Verified date: March 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: May 30, 2029
• Est. primary completion date: May 30, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• Venetoclax
Tablet; Oral

Locations

Country	Name	City	State
Australia	Monash Medical Centre /ID# 201263	Clayton	Victoria
Australia	Concord Repatriation General Hospital /ID# 201261	Concord	New South Wales
Australia	St George Hospital /ID# 206484	Kogarah	New South Wales
China	Peking Union Medical College Hospital /ID# 156576	Beijing	Beijing
China	Peking University People's Hospital /ID# 156575	Beijing	Beijing
China	The First Hospital of Jilin University /ID# 156532	Changchun	Jilin
China	Xiangya Hospital Central South University /ID# 208913	Changsha	Hunan
China	The General Hospital of Western Theater Command PLA /ID# 159145	Chengdu	Sichuan
China	West China Hospital, Sichuan University /ID# 156537	Chengdu	Sichuan
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 First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578	Hangzhou	Zhejiang
China	Anhui Provincial Cancer Hospital /ID# 209458	Hefei	Anhui
China	Shandong Provincial Hospital /ID# 156574	Jinan	Shandong
China	The First Affiliated Hospital of Nanchang University /ID# 159142	Nanchang	Jiangxi
China	Jiangsu Province Hospital /ID# 156577	Nanjing	Jiangsu
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572	Shanghai	Shanghai
China	The Second Hospital of Hebei Medical University /ID# 159143	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University /ID# 156536	Suzhou	Jiangsu
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	Tongji Hospital Tongji Medical College of HUST /ID# 156589	Wuhan	Hubei
China	Henan Cancer Hospital /ID# 156573	Zhengzhou	Henan
New Zealand	Christchurch Hospital /ID# 201650	Christchurch	Canterbury
New Zealand	North Shore Hospital /ID# 204637	Takapuna	Auckland
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	National Taiwan University Hospital /ID# 210733	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital /ID# 203636	Taoyuan City

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

Australia,  China,  New Zealand,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Measured up to 2 years after the last participant has enrolled in the study.
Secondary	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.	Measured up to 2 years after the last participant has enrolled into the study.
Secondary	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	Measured up to 2 years after the last participant has enrolled into the study.
Secondary	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.	Measured up to 5 years after the last participant has enrolled into the study.
Secondary	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.	Measured up to 5 years after the last participant has enrolled into the study.
Secondary	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).	Measured up to 5 years after the last participant has enrolled into the study.
Secondary	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.	Measured up to 2 years after the last participant has enrolled into the study.
Secondary	Overall Survival (OS)	OS is defined as number of days from the date of first dose to the date of death.	Measured up to 5 years after the last participant has enrolled into the study.

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