A Study to Evaluate the Efficacy of Venetoclax in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL) Including Those With 17p Deletion or TP53 Mutation or Those Who Have Received a Prior B-cell Receptor Inhibitor. (VENICE I)

• ClinicalTrials.gov Identifier: NCT02756611
• Recruitment Status: Active, not recruiting
• First Posted: April 29, 2016
• Last Update Posted: December 11, 2019
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: April 26, 2016
• First Posted Date: April 29, 2016
• Last Update Posted Date: December 11, 2019
• Actual Study Start Date: June 22, 2016
• Estimated Primary Completion Date: April 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2016)

Complete Remission Rate (CR + CRi) as assessed by the investigator [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]

The proportion of participants achieving a CR or CRi as their best response (per the investigator assessment) based on 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02756611 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 7, 2018)

• Time to Progression (TTP) [ Time Frame: Measured up to 2 years after the last subject has enrolled in the study. ]
  TTP is defined as the number of days from the date of first dose or enrollment if not dosed to the date of earliest disease progression.
• Overall Response Rate (ORR) [ Time Frame: Measured up to 2 years after the last subject 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 IWCLL NCI-WG criteria.
• Duration of Overall Response (DoR) [ Time Frame: Measured up to 2 years after the last subject 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.
• CR Rate (CR + CRi) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  CR + CRi in previously treated B-Cell receptor inhibitor (BCRi) subjects assessed based on the 2008 Modified IWCLL NCI-WG criteria.
• Overall Survival (OS) [ Time Frame: Measured up to 2 years after the last subject has enrolled into the study. ]
  OS is defined as number of days from the date of first dose to the date of death for all dosed subjects.
• Progression-Free Survival (PFS) [ Time Frame: Measured up to 2 years after the last subject 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 or death.
• Rate of Minimal Residual Disease (MRD) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  The rate is defined as the proportion of participants who had MRD negativity status.

Original Secondary Outcome Measures (submitted: April 27, 2016)

• Overall Response Rate (ORR) [ Time Frame: Measured up to 2 years after the last subject 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 IWCLL NCI-WG criteria.
• Duration of Overall Response (DoR) [ Time Frame: Measured up to 2 years after the last subject 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 subject has enrolled in the study. ]
  TTP is defined as the number of days from the date of first dose or enrollment if not dosed to the date of earliest disease progression.
• Progression-Free Survival (PFS) [ Time Frame: Measured up to 2 years after the last subject 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 or death.
• Overall Survival (OS) [ Time Frame: Measured up to 2 years after the last subject has enrolled into the study. ]
  OS is defined as number of days from the date of first dose to the date of death for all dosed subjects.
• CR Rate (CR + CRi) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  CR + CRi in previously treated B-Cell receptor inhibitor (BCRi) subjects assessed based on the 2008 Modified IWCLL NCI-WG criteria.
• Rate of Minimal Residual Disease (MRD) [ Time Frame: When all participants have completed Week 48 disease assessment, or after all enrolled participants have discontinued venetoclax, whichever is earlier. ]
  The rate is defined as the proportion of participants who had MRD negativity status.

Current Other Pre-specified Outcome Measures (submitted: April 27, 2016)

• Functional Assessment of Cancer Therapy - Leukemia Questionnaire (FACT-Leu) [ Time Frame: Up to Week 108 ]
  The FACT-Leu is a 44-item, leukemia-specific questionnaire designed to assess patient health-related quality of life (HRQoL) and leukemia-specific symptoms.
• Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F) [ Time Frame: Up to Week 108 ]
  The FACIT-F questionnaire measures fatigue and its effect on functioning and daily activities. The FACIT-F has 13 items answered on a 5-point rating scale based on a 7-day recall period.
• EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) [ Time Frame: Up to Week 108 ]
  Five items in the EQ-5D-5L questionnaire (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) are rated on 5 levels of severity.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy of Venetoclax in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL) Including Those With 17p Deletion or TP53 Mutation or Those Who Have Received a Prior B-cell Receptor Inhibitor.
• Official Title: Open-Label, Single Arm, Phase 3b, Multi-Center Study Evaluating the Efficacy of Venetoclax (ABT-199) in Relapsed/Refractory Subjects With Chronic Lymphocytic Leukemia (CLL)
• Brief Summary: The purpose of this open-label, single-arm study is to evaluate the efficacy of venetoclax monotherapy in approximately 250 participants with relapsed/refractory CLL including those with the 17p deletion or TP53 mutation (assessed by local lab) OR those who have received prior treatment with a B-cell receptor inhibitor. 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 400 mg. 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

Intervention

Drug: Venetoclax

Tablets

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 10, 2019): 258
• Original Estimated Enrollment (submitted: April 27, 2016): 250
• Estimated Study Completion Date: April 3, 2022
• Estimated Primary Completion Date: April 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2
• Participant has relapsed/refractory disease (received at least 1 prior therapy)

• Participant has diagnosis of CLL that meets published 2008 Modified IWCLL NCI-WG Guidelines and:

  • has an indication for treatment according to the 2008 Modified IWCLL NCI-WG criteria
  • has clinically measurable disease (lymphocytosis greater than 5 × 109/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam)

• In addition, participants:

  • with or without 17p deletion or TP53 mutation, assessed by a local laboratory in bone marrow or peripheral blood AND/OR
  • may have been previously treated with a prior B-cell receptor inhibitor
• Participant must have adequate bone marrow function, coagulation profile, renal, and hepatic function, per laboratory reference range at Screening

Exclusion Criteria:

• Participant has developed Richter's transformation or Prolymphocytic leukemia
• 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
• Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura despite low dose corticosteroids

• Participant has undergone an allogeneic stem cell transplant grade 2:

  • Any anti-cancer therapy including chemotherapy, or radiotherapy;
  • Investigational therapy, including targeted small molecule agents
• Participant is human immunodeficiency virus (HIV) positive
• Participant has known allergy to both xanthine oxidase inhibitors and rasburicase

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: Austria, Belgium, Canada, Denmark, Finland, France, Germany, Greece, Ireland, Israel, Italy, Netherlands, Norway, Portugal, Puerto Rico, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02756611
• Other Study ID Numbers: M15-550; 2015-003667-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• 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