A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent). (VENICE II)

• ClinicalTrials.gov Identifier: NCT02980731
• Recruitment Status: Active, not recruiting
• First Posted: December 2, 2016
• Last Update Posted: December 11, 2019
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 30, 2016
• First Posted Date: December 2, 2016
• Last Update Posted Date: December 11, 2019
• Actual Study Start Date: December 13, 2016
• Estimated Primary Completion Date: November 11, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2016)

Change in Global Health Status/Quality of Life (GHS/QoL) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) [ Time Frame: From Screening (Baseline) up to Week 48 ]

EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small. A change of 10 - 20 points is considered a moderate change.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02980731 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 5, 2018)

• Complete Remission rate (complete remission [CR] + complete remission with incomplete marrow recovery [CRi]) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  Complete remission rate (CR + CRi) defined as the proportion of subjects achieving a CR or CRi as their best response (per the investigator assessment) based on IWCLL NCI -WG criteria.
• Duration of Overall Response (DOR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  DoR is defined as the number of days from the date of first response (CR, CRi, nPR, or PR) to the earliest recurrence or progressive disease.
• Duration of Progression-Free Survival (PFS) [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
  PFS defined as the number of days from the date of first dose of venetoclax to the date of disease progression or death, whichever occurs first.
• Time to Progression (TTP) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  TPP defined as the number of days from the date of first dose of venetoclax to the date of disease progression.
• EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  The EQ-5D-5L has five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. These dimensions are measured on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The scores for the 5 dimensions are used to compute a single utility index score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual. The EQ-5D-5L also contains a visual analog scale (VAS) to assess the subject's overall health.
• Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16), [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of HRQoL important in CLL. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." A negative change in score from baseline represents an improvement in symptoms. A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
• Overall Survival (OS) [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
  OS defined as number of days from the date of first dose of venetoclax to the date of death for all dosed participants.
• Change in the remaining subscales/items from the EORTC QLQ-C30. [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and difficulties). Subjects rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
• Overall Response Rate (ORR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  ORR assessed as the proportion of participants with an overall response (CR + CRi + Nodular Partial Remission [nPR] + Partial Remission [PR]) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group Guidelines (IWCLL NCI-WG) criteria.

Original Secondary Outcome Measures (submitted: November 30, 2016)

• Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16), [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of HRQoL important in CLL. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." A negative change in score from baseline represents an improvement in symptoms. A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
• EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  The EQ-5D-5L has five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. These dimensions are measured on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The scores for the 5 dimensions are used to compute a single utility index score ranging from zero (0.0) to 1 (1.0) representing the general health status of the individual. The EQ-5D-5L also contains a visual analog scale (VAS) to assess the subject's overall health.
• Change in the remaining subscales/items from the EORTC QLQ-C30. [ Time Frame: From Screening (Baseline; Day 0) up to Week 48 ]
  The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and difficulties). Subjects rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
• Complete Remission rate (complete remission [CR] + complete remission with incomplete marrow recovery [CRi]) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  Complete remission rate (CR + CRi) defined as the proportion of subjects achieving a CR or CRi as their best response (per the investigator assessment) based on IWCLL NCI -WG criteria.
• Overall Response Rate (ORR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  ORR assessed as the proportion of participants with an overall response (CR + CRi + Nodular Partial Remission [nPR] + Partial Remission [PR]) based on the 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group Guidelines (IWCLL NCI-WG) criteria.
• Duration of Overall Response (DOR) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  DoR is defined as the number of days from the date of first response (CR, CRi, nPR, or PR) to the earliest recurrence or progressive disease.
• Time to Progression (TTP) [ Time Frame: Measured up to 2 years after the last participant has enrolled in the study. ]
  TPP defined as the number of days from the date of first dose of venetoclax to the date of disease progression.
• Duration of Progression-Free Survival (PFS) [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
  PFS defined as the number of days from the date of first dose of venetoclax to the date of disease progression or death, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Measured up to 2 years after the last participant has enrolled into the study. ]
  OS defined as number of days from the date of first dose of venetoclax to the date of death for all dosed participants.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating the Impact of Venetoclax on the Quality of Life for Subjects With Relapsed (Your Cancer Has Come Back) or Refractory (no Response to Previous Cancer Treatments) Chronic Lymphocytic Leukemia (CLL) While Receiving Venetoclax Monotherapy (a Single Agent).
• Official Title: Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Impact of Venetoclax on the Quality of Life of Relapsed/Refractory Subjects With Chronic Lymphocytic Leukemia (CLL)
• Brief Summary: The purpose of this open-label, single-arm study is to evaluate the impact of venetoclax on the quality of life of participants including those with with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL; a type of cancer affecting the blood and the bone marrow) with or without the 17p deletion or TP53 mutation, including subjects with an unknown status, as well as R/R CLL subjects who have been previously treated with B-cell receptor inhibitor (BCRi) therapy. The starting dose of venetoclax is 20 mg once daily. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400mg. Participants may continue receiving venetoclax for up to 2 years. After the treatment period, participants may continue on into a 2-year follow-up period.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia (CLL)

Intervention

Drug: Venetoclax

Tablet

Other Name: ABT-199

Study Arms

Experimental: Venetoclax

Venetoclax will be administered orally 20 mg once daily (QD) beginning with a dose-titration phase, and then escalated up to 400 mg QD.

Intervention: Drug: Venetoclax

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 18, 2018): 210
• Original Estimated Enrollment (submitted: November 30, 2016): 200
• Estimated Study Completion Date: June 26, 2022
• Estimated Primary Completion Date: November 11, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
• Participant has relapsed/refractory disease (received at least one prior therapy).

• Diagnosis of CLL that meets published 2008 Modified International Workshop on CLL National Cancer Institute - Working Group (IWCLL NCI-WG) Guidelines and:

  • has an indication for treatment according to the 2008 Modified IWCLL NCI-WG Guidelines
  • has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam)
  • with or without 17p deletion or TP53 mutation
  • may have been previously treated with a prior B-cell receptor inhibitor therapy
• Adequate bone marrow function.

Exclusion Criteria:

• Participant has developed Richter's transformation or Prolymphocytic leukemia (PLL).
• Participant has previously received venetoclax.

• History of active malignancies other than CLL within the past 2 years prior to first dose of venetoclax, with the exception of:

  • adequately treated in situ carcinoma of the cervix uteri
  • adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
  • previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
• Active and uncontrolled autoimmune cytopenias (within 2 weeks prior to screening), including autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), despite low dose corticosteroids.
• Prior allogeneic stem cell transplant.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Bulgaria, Australia, Hong Kong, Hungary, Mexico, New Zealand, Poland, Russian Federation, Taiwan
• Removed Location Countries: Romania

Administrative Information

• NCT Number: NCT02980731
• Other Study ID Numbers: M15-889; 2016-001097-15 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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 and 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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 (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: December 2019