VENICE II: 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).

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT02980731

Collaborator

(none)

200

Enrollment

Locations

Arm

60.5

Actual Duration (Months)

6.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia (CLL)	Drug: Venetoclax	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Dec 13, 2016

Actual Primary Completion Date :

Dec 29, 2021

Actual Study Completion Date :

Dec 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Venetoclax Tablet Other Names: ABT-199

Arm

Intervention/Treatment

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.

Drug: Venetoclax

Tablet

Other Names:

ABT-199

Outcome Measures

Primary Outcome Measures

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) [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.

Secondary Outcome Measures

Complete Remission rate (complete remission [CR] + complete remission with incomplete marrow recovery [CRi]) [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) [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) [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) [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) [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), [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) [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. [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Italiano La Plata /ID# 150812	La Plata	Buenos Aires	Argentina	1902
2	Fundaleu /Id# 150811	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1114
3	Cemic /Id# 150810	Ciudad Autonoma de Buenos Aire	Ciuadad Autonoma De Buenos Aires	Argentina	1431
4	Sanatorio Allende /ID# 150813	Cordoba		Argentina	5000
5	St George Hospital /ID# 154212	Kogarah	New South Wales	Australia	2217
6	Liverpool Hospital /ID# 154950	Liverpool	New South Wales	Australia	2170
7	Gold coast University Hospital /ID# 150833	SouthPort	Queensland	Australia	4215
8	Peter MacCallum Cancer Ctr /ID# 154948	Melbourne	Victoria	Australia	3000
9	Perth Blood Institute Ltd /ID# 154949	Nedlands	Western Australia	Australia	6009
10	UMHAT Alexandrovska EAD /ID# 162987	Sofiya	Sofia	Bulgaria	1431
11	UMHAT Sveti Georgi /ID# 161594	Plovdiv		Bulgaria	4002
12	UMHAT Sveti Ivan Rilski /ID# 163280	Sofia		Bulgaria	1431
13	SHAT Hematologic Diseases /ID# 161592	Sofia		Bulgaria	1756
14	Prince of Wales Hospital /ID# 150837	Hong Kong		Hong Kong	999077
15	Queen Mary Hospital /ID# 150836	Hong Kong		Hong Kong	999077
16	Semmelweis Egyetem /ID# 150792	Budapest		Hungary	1085
17	Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 152842	Budapest		Hungary	1097
18	Centro de Investigacion Clínica Chapultepec SA de CV /ID# 163641	Morelia	Michoacan	Mexico	58260
19	Hospital Universitario Dr. Jose Eleuterio Gonzalez /ID# 150821	Monterrey	Nuevo Leon	Mexico	64460
20	Middlemore Clinical Trials /ID# 161526	Papatoetoe	Auckland	New Zealand	2025
21	North Shore Hospital /ID# 157626	Takapuna	Auckland	New Zealand	0622
22	Wellington Regional Hospital /ID# 157627	Newtown	Wellington	New Zealand	6021
23	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopern /ID# 150880	Lodz	Lodzkie	Poland	93-513
24	Instytut Hematologii i Transfuzjologii /ID# 150878	Warszawa	Mazowieckie	Poland	02-776
25	Szpitale Pomorskie Sp. z o.o /ID# 164097	Gdynia	Pomorskie	Poland	81-519
26	SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 150877	Chorzow	Slaskie	Poland	41-500
27	Federal State Budgetary Scientific Institution N.N. Blokhin /ID# 166610	Moscow	Moskva	Russian Federation	115478
28	Moscow State budget healthcare /ID# 154806	Moscow	Moskva	Russian Federation	125284
29	Regional Oncological Dispensary /ID# 154202	Penza	Penzenskaya Oblast	Russian Federation	440071
30	Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 154213	Moscow		Russian Federation	125167
31	China Medical University Hospital /ID# 150839	Taichung City		Taiwan	40447
32	National Taiwan University Hospital /ID# 150838	Taipei City		Taiwan	100
33	Taipei Veterans General Hosp /ID# 153803	Taipei City		Taiwan	11217