A Study to Evaluate the Efficacy of Venetoclax Monotherapy in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL)

AbbVie258 enrolled

Overview

The purpose of this study is to evaluate the efficacy of venetoclax monotherapy in participants with relapsed/refractory CLL with or without the 17p deletion or TP53 mutation, including those who have received prior treatment with a B-cell receptor inhibitor.

Following the Screening period, all eligible participants initiate venetoclax on a once daily (QD) dosing schedule. To mitigate the risk for tumor lysis syndrome (TLS), dosing will start with a 5-week dose titration phase. Participants may receive venetoclax for up to 2 years provided they continue to tolerate the drug, have no evidence of disease progression (based on investigator assessment), do not have unacceptable toxicity and do not meet any of the criteria for subject discontinuation. In countries where venetoclax is not commercially available, participants who continued to derive benefit after 2 years of treatment may extend their treatment for up to 2 additional years in an extended access phase. Participants in the extended access phase of this study who continue to derive benefit from venetoclax after the 2-year extension and are transferring to the venetoclax extension study, Study M19-388 (NCT03844048), may remain in Extended Access for up to 1 additional year or until the extension study is approved and initiated at the site, whichever is sooner.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

258

Conditions

Chronic Lymphocytic Leukemia

Interventions

VenetoclaxDRUG

Tablets for oral administration

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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 International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute Working Group (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 × 10\^9/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 are eligible * 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 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 * Treatment with any of the following within five half-lives or 14 days (if half-life unknown) as applicable prior to the first dose of venetoclax, or clinically significant adverse effect(s)/toxicity(s) of the previous therapy have not resolved to \< National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 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

Locations (67)

Outcomes

Primary Outcomes

Complete Remission Rate in Participants Not Previously Treated With BCRi Therapy - Primary Analysis

Complete remission rate is defined as the percentage of participants achieving a best response of complete remission (CR) or complete remission with incomplete marrow recovery (CRi) assessed by the investigator based on 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria. CR required all of the following: * Peripheral blood lymphocytes \< 4000/μL * Absence of lymphadenopathy by physical examination and computed tomography scan * No hepatomegaly or splenomegaly by physical examination * Absence of disease or constitutional symptoms (unexplained fevers \> 38°C, drenching night sweats, \> 10% weight loss in last 6 months) * Blood counts above the following: * Neutrophils \> 1500/μL * Platelets \> 100,000/μL * Hemoglobin \> 110 g/L * Bone marrow at least normocellular for age, \< 30% lymphocytes. CRi was defined as for CR but with persistent cytopenia apparently unrelated to CLL but related to drug toxicity.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Secondary Outcomes

Complete Remission Rate in Participants Previously Treated With BCRi Therapy - Primary Analysis

Complete remission rate is defined as the percentage of participants achieving a best response of complete remission (CR) or complete remission with incomplete marrow recovery (CRi) assessed by the investigator based on 2008 modified IWCLL NCI-WG criteria. CR required all of the following: * Peripheral blood lymphocytes \< 4000/μL * Absence of lymphadenopathy by physical examination and computed tomography scan * No hepatomegaly or splenomegaly by physical examination * Absence of disease or constitutional symptoms (unexplained fevers \> 38°C, drenching night sweats, \> 10% weight loss in last 6 months) * Blood counts above the following: * Neutrophils \> 1500/μL * Platelets \> 100,000/μL * Hemoglobin \> 110 g/L * Bone marrow at least normocellular for age, \< 30% lymphocytes CRi was defined as for CR but with persistent cytopenia apparently unrelated to CLL but related to drug toxicity.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Norton Cancer Institute /ID# 149788

Louisville, Kentucky, United States

St. Agnes Cancer Center /ID# 149782

Baltimore, Maryland, United States

Hackensack Univ Med Ctr /ID# 151574

Hackensack, New Jersey, United States

Utah Cancer Specialists /ID# 151604

Salt Lake City, Utah, United States

Cancer Care Northwest /ID# 151605

Spokane, Washington, United States

West Virginia Univ School Med /ID# 151602

Morgantown, West Virginia, United States

LKH-Univ. Klinikum Graz /ID# 147547

Graz, Austria

LKH Salzburg and Paracelsus /ID# 147549

Salzburg, Austria

Hanusch Krankenhaus der WGKK /ID# 147548

Vienna, Austria

Cliniques Universitaires Saint Luc /ID# 147388

Woluwe-Saint-Lambert, Brussels Capital, Belgium

...and 57 more locations

Overall Response Rate (ORR) - Primary Analysis

Overall response rate was defined as the percentage of participants with an overall best response of CR, CRi, nodular partial remission (nPR), or confirmed partial remission (PR) based on the 2008 modified IWCLL NCI-WG criteria assessed by the investigator. CR and CRi are defined above. nPR is defined as for CR but bone marrow nodules could be identified histologically. For PR at least 2 of the following must be met: * 50% decrease in peripheral blood lymphocyte count from the Baseline value; * 50% reduction in lymphadenopathy; * 50% reduction in the size of the liver and/or spleen (if abnormal prior to therapy); In addition at least 1 of the following criteria must be met: * Neutrophils \> 1,500/μL or ≥ 50% improvement over Baseline; * Platelets \> 100,000/μL or ≥ 50% improvement over Baseline; * Hemoglobin \> 11.0 g/dL or ≥ 50% improvement over Baseline without transfusions or exogenous growth factors. PR must have been confirmed at least 7 weeks later.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Duration of Overall Response (DOR) - Primary Analysis

Duration of response was defined as the time from the date of first response (CR, CRi, nPR, or PR) to the earliest date that progressive disease (PD) was objectively documented (radiographic or clinical) or death. Duration of response was analyzed by Kaplan-Meier (K-M) methodology. If a participant was still responding the data were censored at the date of the last available disease assessment prior to the data cutoff date.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Time to Progression (TTP) - Primary Analysis

Time to progression was defined as the time from the date of first dose of venetoclax to the date of earliest PD (radiographic or clinical). Participants who did not experience disease progression were censored at the date of the last available disease assessment prior to the data cutoff date; participants with no post-baseline disease assessments were censored at the first dose date plus 1 day. Time to progression was estimated using Kaplan-Meier methodology.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Progression-Free Survival (PFS) - Primary Analysis

Progression-free survival (PFS) was defined as the time from the date of first dose of venetoclax to the date of earliest PD (radiographic or clinical) or death. Participants who did not experience disease progression or death were censored at the date of the last available disease assessment prior to the data cutoff date; participants with no post-baseline tumor assessment or clinical assessment for progression were censored at the date of first dose plus 1 day. Progression-free survival was analyzed by Kaplan-Meier methodology.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Overall Survival (OS) - Primary Analysis

Overall survival (time to death) was defined as the time from the first dose date of venetoclax to the date of death. If a participant had not died the data were censored at the date when they were last known to be alive prior to the cutoff date. Overall survival was analyzed using Kaplan-Meier methodology.

Time frame: From first dose of study drug until the last participant completed Week 48 assessments (data cut-off date 30 June 2019); overall median time on follow-up was 23.2 months.

Change From Baseline in Functional Assessment of Cancer Therapy - Leukemia Questionnaire (FACT-Leu)

The FACT-Leu is a 44-item, leukemia-specific questionnaire designed to assess health-related quality of life (HRQoL) and leukemia-specific symptoms using a core set of questions (Functional Assessment of Cancer Therapy-General; FACT-G), and a cancer site-specific leukemia subscale. Questions are scored on a scale from 0 (not at all) to 4 (very much). FACT-G consists of 27 general items divided into 4 primary HRQoL domains: Physical Well-being (PWB; 7 items; score range 0-28), Social/Family Well-being (SWB; 7 items; score range 0-28), Emotional Well-being (EWB; 6 items; score range 0-24), Functional Well-being (FWB; 7 items; score range 0-28). The leukemia subscale consists of 17 items (score range 0-68) that assess patient concerns relating to leukemia. Three summary scales were calculated: FACT-Trial Outcome Index composed of the PWB, FWB, and leukemia subscale (score range 0-124); FACT-G (score range 0-108) and the FACT-Leu Total (range 0-176). Higher scores reflect better HRQoL.

Time frame: Baseline and Weeks 48 and 108

Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)

The FACIT-Fatigue questionnaire measures fatigue and its effect on functioning and daily activities. The FACIT-Fatigue includes 13 items answered on a 5-point rating scale based on a 7-day recall period. Scores range from 0 to 52, with lower scores reflecting greater fatigue.

Time frame: Baseline and Weeks 48 and 108

Change From Baseline in EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) Health Index Score

The EQ-5D-5L is a generic measure of health status consisting of two parts: a descriptive system consisting of 5 items and a visual analog scale (VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The participant is asked to rate each dimension on 5 levels of severity (1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems). The scores for the 5 dimensions are used to compute a single health utility index score representing the general health status of the individual. The health index score ranges from zero (defined as a health state equivalent to being dead) to 1 (full health).

Time frame: Baseline and Weeks 48 and 108

Change From Baseline in EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) Visual Analog Scale Score

The EQ-5D-5L is a generic measure of health status consisting of two parts, a descriptive system consisting of 5 items and a visual analog scale (VAS). The VAS assesses the participant's self-rated overall health on a scale from 0 (worst health imaginable) to 100 (best health imaginable).

Time frame: Baseline and Weeks 48 and 108