Clinical trial NCT02980731: 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) (VENICE II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia (CLL)
Keywords: Relapsed CLL
Refractory CLL
17p deletion
TP53 gene
B-Cell receptor inhibitor (BCRi)
European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
Overall response rate (ORR)
Duration of overall response (DOR)
Complete remission rate (CR + CRi)
Progression-free survival (PFS)
Overall survival (OS)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-12-02
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, single-arm study was 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 participants with an unknown status, as well as R/R CLL participants who had been previously treated with B-cell receptor inhibitor (BCRi) therapy. The starting dose of venetoclax was 20 mg once daily. The dose must have been gradually increased over a period of 5 weeks up to the daily dose of 400 mg. Participants may have continued receiving venetoclax for up to 2 years. After the treatment period, participants may have continued on into a 2-year follow-up period.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 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

Primary outcomes:
measure: Mean Change From Baseline to Week 48 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)
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: Mean Change From Baseline 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)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Physical Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Role Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Emotional Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Cognitive Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Social Functioning Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Nausea and Vomiting Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Pain Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Dyspnea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Insomnia Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Appetite Loss Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Constipation Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Diarrhea Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Financial Difficulties Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Fatigue Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Treatment Side Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Disease Effects Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Infection Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Social Problems Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in Future Health Subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Lymphocytic Leukemia Module (EORTC QLQ-CLL16)
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale Score
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Mean Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Health Index Score
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, Final visit (at study drug discontinuation and/or upon discontinuation from the study, up to Week 108)
measure: Complete Remission Rate (Complete Remission [CR] + Complete Remission With Incomplete Marrow Recovery [CRi])
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
measure: Overall Response Rate (ORR)
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
measure: Duration of Overall Response (DOR)
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
measure: Time to Progression (TTP)
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
measure: Progression-Free Survival (PFS)
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
measure: Overall Survival (OS)
timeFrame: From the first dose of study drug until the last participant completed the Week 48 assessments; median time on follow-up was 184 weeks
Other outcomes:
Locations:
city: La Plata
country: Argentina
facility: Hospital Italiano La Plata /ID# 150812
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Fundaleu /Id# 150811
state: Ciuadad Autonoma De Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Cemic /Id# 150810
state: Ciuadad Autonoma De Buenos Aires
city: Cordoba
country: Argentina
facility: Sanatorio Allende /ID# 150813
city: Kogarah
country: Australia
facility: St George Hospital /ID# 154212
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital /ID# 154950
state: New South Wales
city: SouthPort
country: Australia
facility: Gold coast University Hospital /ID# 150833
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 154948
state: Victoria
city: Nedlands
country: Australia
facility: Perth Blood Institute Ltd /ID# 154949
state: Western Australia
city: Sofiya
country: Bulgaria
facility: UMHAT Alexandrovska EAD /ID# 162987
state: Sofia
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi /ID# 161594
city: Sofia
country: Bulgaria
facility: UMHAT Sveti Ivan Rilski /ID# 163280
city: Sofia
country: Bulgaria
facility: SHAT Hematologic Diseases /ID# 161592
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital /ID# 150837
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital /ID# 150836
city: Budapest
country: Hungary
facility: Semmelweis Egyetem /ID# 150792
city: Budapest
country: Hungary
facility: Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152842
city: Morelia
country: Mexico
facility: Centro de Investigacion Clínica Chapultepec SA de CV /ID# 163641
state: Michoacan
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez /ID# 150821
state: Nuevo Leon
city: Papatoetoe
country: New Zealand
facility: Middlemore Clinical Trials /ID# 161526
state: Auckland
city: Takapuna
country: New Zealand
facility: North Shore Hospital /ID# 157626
state: Auckland
city: Newtown
country: New Zealand
facility: Wellington Regional Hospital /ID# 157627
state: Wellington
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 150880
state: Lodzkie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii /ID# 150878
state: Mazowieckie
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o /ID# 164097
state: Pomorskie
city: Chorzow
country: Poland
facility: SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 150877
state: Slaskie
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution N.N. Blokhin /ID# 166610
state: Moskva
city: Moscow
country: Russian Federation
facility: Moscow State budget healthcare /ID# 154806
state: Moskva
city: Penza
country: Russian Federation
facility: Regional Oncological Dispensary /ID# 154202
state: Penzenskaya Oblast
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 154213
city: Taichung City
country: Taiwan
facility: China Medical University Hospital /ID# 150839
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 150838
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 153803
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References:
citation: Cochrane T, Enrico A, Gomez-Almaguer D, Hadjiev E, Lech-Maranda E, Masszi T, Nikitin E, Robak T, Weinkove R, Wu SJ, Sail KR, Pesko J, Pai M, Komlosi V, Anderson MA. Impact of venetoclax monotherapy on the quality of life of patients with relapsed or refractory chronic lymphocytic leukemia: results from the phase 3b VENICE II trial. Leuk Lymphoma. 2022 Feb;63(2):304-314. doi: 10.1080/10428194.2021.1986217. Epub 2021 Oct 11.