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

A Phase 2 Open-Label Study of the Efficacy of Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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).

Study Overview

• Status: Recruiting
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)
• Intervention / Treatment: Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital /ID# 201261
    • Kogarah, New South Wales, Australia, 2217
      • Recruiting
      • St George Hospital /ID# 206484
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre /ID# 201263
• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Recruiting
      • Anhui Provincial Cancer Hospital /ID# 209458
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital /ID# 156575
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital /ID# 156576
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital /ID# 156579
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • Guangdong Provincial People's Hospital /ID# 160509
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital of Southern Medical University /ID# 156571
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Completed
      • The Second Hospital of Hebei Medical University /ID# 159143
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital /ID# 156573
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital Tongji Medical College of HUST /ID# 156589
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Xiangya Hospital Central South University /ID# 208913
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital /ID# 156577
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University /ID# 156536
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University /ID# 159142
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Hospital of Jilin University /ID# 156532
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital /ID# 156574
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Recruiting
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 156572
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University /ID# 156537
    • Chengdu, Sichuan, China, 610083
      • Recruiting
      • The General Hospital of Western Theater Command PLA /ID# 159145
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 157762
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital /ID# 156542
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 156578
• New Zealand
  • Auckland
    • Takapuna, Auckland, New Zealand, 0622
      • Recruiting
      • North Shore Hospital /ID# 204637
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Recruiting
      • Christchurch Hospital /ID# 201650
• Taiwan
  • Changhua City, Changhua County, Taiwan, 50006
    • Completed
    • Changhua Christian Hospital /ID# 202768
  • Kaohsiung, Taiwan, 807
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 202765
  • Taichung, Taiwan, 40447
    • Recruiting
    • China Medical University Hospital /ID# 202767
  • Taipei City, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital /ID# 210733
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Linkou Chang Gung Memorial Hospital /ID# 203636

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Venetoclax; Participants with 17p deletion status will receive various doses of venetoclax once daily (QD).	Drug: Venetoclax; Tablet; Oral; Other Names: Venclexta; ABT-199; GDC-0199
Experimental: Cohort 2: 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).	Drug: Venetoclax; Tablet; Oral; Other Names: Venclexta; ABT-199; GDC-0199

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2017
• Primary Completion (Estimated): May 30, 2029
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimated): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Leukemia; Venetoclax; Venclexta; 17p deletion; Lymphoproliferative Disorders; Small Lymphocytic Lymphoma (SLL); Relapsed chronic lymphocytic leukemia (CLL); Refractory chronic lymphocytic leukemia (CLL)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M14-728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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