Clinical trial NCT02756611: A Study to Evaluate the Efficacy of Venetoclax Monotherapy in Relapsed/Refractory Participants With Chronic Lymphocytic Leukemia (CLL)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: Oncology
Chronic Lymphocytic Leukemia
17p Deletion
TP53 Mutation
Relapsed
Refractory
B-Cell receptor inhibitor
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-04-29
Enrollment: 258
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 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.

Detailed description: 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.

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 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

Primary outcomes:
measure: Complete Remission Rate in Participants Not Previously Treated With BCRi Therapy - Primary Analysis
timeFrame: 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:
measure: Complete Remission Rate in Participants Previously Treated With BCRi Therapy - Primary Analysis
timeFrame: 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.
measure: Overall Response Rate (ORR) - Primary Analysis
timeFrame: 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.
measure: Duration of Overall Response (DOR) - Primary Analysis
timeFrame: 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.
measure: Time to Progression (TTP) - Primary Analysis
timeFrame: 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.
measure: Progression-Free Survival (PFS) - Primary Analysis
timeFrame: 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.
measure: Overall Survival (OS) - Primary Analysis
timeFrame: 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.
measure: Change From Baseline in Functional Assessment of Cancer Therapy - Leukemia Questionnaire (FACT-Leu)
timeFrame: Baseline and Weeks 48 and 108
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue)
timeFrame: Baseline and Weeks 48 and 108
measure: Change From Baseline in EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) Health Index Score
timeFrame: Baseline and Weeks 48 and 108
measure: Change From Baseline in EuroQoL 5 Dimension 5 Level Questionnaire (EQ-5D-5L) Visual Analog Scale Score
timeFrame: Baseline and Weeks 48 and 108
Other outcomes:
measure: Complete Remission Rate in Participants Not Previously Treated With BCRi Therapy - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Complete Remission Rate in Participants Previously Treated With BCRi Therapy - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Overall Response Rate (ORR) - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Duration of Overall Response (DOR) - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Time to Progression (TTP) - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Progression-Free Survival (PFS) - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Overall Survival (OS) - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
measure: Minimal Residual Disease (MRD) Negativity Rate - Primary Analysis
timeFrame: 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.
measure: Minimal Residual Disease (MRD) Negativity Rate - Final Analysis
timeFrame: From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.
Locations:
city: Louisville
country: United States
facility: Norton Cancer Institute /ID# 149788
state: Kentucky
city: Baltimore
country: United States
facility: St. Agnes Cancer Center /ID# 149782
state: Maryland
city: Hackensack
country: United States
facility: Hackensack Univ Med Ctr /ID# 151574
state: New Jersey
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists /ID# 151604
state: Utah
city: Spokane
country: United States
facility: Cancer Care Northwest /ID# 151605
state: Washington
city: Morgantown
country: United States
facility: West Virginia Univ School Med /ID# 151602
state: West Virginia
city: Graz
country: Austria
facility: LKH-Univ. Klinikum Graz /ID# 147547
city: Salzburg
country: Austria
facility: LKH Salzburg and Paracelsus /ID# 147549
city: Wien
country: Austria
facility: Hanusch Krankenhaus der WGKK /ID# 147548
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 147388
state: Bruxelles-Capitale
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 147387
city: Vancouver
country: Canada
facility: BC Cancer Agency /ID# 153091
state: British Columbia
city: Halifax
country: Canada
facility: Qe Ii Hsc /Id# 147460
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Clinic /ID# 149152
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Ctr /ID# 147462
state: Ontario
city: Quebec City
country: Canada
facility: CHU de Quebec-Universite Laval /ID# 150299
state: Quebec
city: Herlev
country: Denmark
facility: Herlev Hospital /ID# 150183
state: Hovedstaden
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital /ID# 147409
state: Midtjylland
city: Turku
country: Finland
facility: Turku University Hospital /ID# 147551
city: Limoges CEDEX 1
country: France
facility: CHU Dupuytren /ID# 147552
state: Franche-Comte
city: Poitiers
country: France
facility: CHU de la miletrie /ID# 147484
state: Poitou-Charentes
city: Bordeaux
country: France
facility: Institut Bergonie /ID# 147482
city: Brest
country: France
facility: CHRU de Brest - Hopital Morvan /ID# 147485
city: Strasbourg
country: France
facility: clinique Sainte Anne /ID# 147556
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis /ID# 147516
city: Frankfurt
country: Germany
facility: Cent fuer Haematologie und Onk /ID# 147511
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH /ID# 164044
city: Mannheim
country: Germany
facility: Mannheimer Onkologiepraxis /ID# 147512
city: Munich
country: Germany
facility: Staedt. Klinikum Schwabing /ID# 147510
city: Athens
country: Greece
facility: General Hospital of Athens Laiko /ID# 147517
state: Attiki
city: Thessaloniki
country: Greece
facility: G. Papanikolaou Hospital /ID# 147518
city: Dublin 8
country: Ireland
facility: St. James's Hospital /ID# 147519
state: Dublin
city: Dublin
country: Ireland
facility: Beaumont Hospital /ID# 147522
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Ctr /ID# 151624
state: Tel-Aviv
city: Nahariya
country: Israel
facility: Galilee Medical Center /ID# 159971
city: Ramat Gan
country: Israel
facility: Sheba Medical Center /ID# 147509
city: Bologna
country: Italy
facility: A.O.U. Policlinico S.Orsola-Malpighi /ID# 147505
state: Emilia-Romagna
city: Rome
country: Italy
facility: AP Romano Umberto I /ID# 147500
state: Lazio
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda /ID# 147503
state: Lombardia
city: Milan
country: Italy
facility: Ospedale San Raffaele IRCCS /ID# 147504
city: Novara
country: Italy
facility: AO Maggiore della Carita /ID# 147499
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum /ID# 147494
state: Noord-Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis /ID# 147495
state: Zuid-Holland
city: Bergen
country: Norway
facility: Haukeland University Hospital /ID# 147382
state: Hordaland
city: Oslo
country: Norway
facility: Rikshospitalet OUS HF /ID# 201812
city: Lisboa
country: Portugal
facility: IPO Lisboa FG, EPE /ID# 147385
city: Porto
country: Portugal
facility: IPO Porto FG, EPE /ID# 147389
city: San Juan
country: Puerto Rico
facility: Puerto Rico Hematology Oncolog /ID# 150003
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 151230
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz /ID# 151231
city: Majadahonda
country: Spain
facility: Hosp Univ Puerta de Hierro /ID# 147391
city: Salamanca
country: Spain
facility: Hospital Clinico Univ de Salamanca /ID# 147392
city: València
country: Spain
facility: Hosp Clin Univ de Valencia /ID# 147396
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Lund /ID# 147439
state: Skane Lan
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset /ID# 150184
state: Uppsala Lan
city: Genève
country: Switzerland
facility: Hopitaux Universitaires de Geneve /ID# 147930
state: Geneve
city: Zurich
country: Switzerland
facility: University Hospital Zurich /ID# 157910
state: Zuerich
city: Bellinzona
country: Switzerland
facility: Ospedale Regional Bellinzona e /ID# 151232
city: Ankara
country: Turkey
facility: Ankara Univ Medical Faculty /ID# 147443
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty /ID# 156040
city: Istanbul
country: Turkey
facility: Vehbi Koc vakfi Amerikan Hasta /ID# 147325
city: Izmir
country: Turkey
facility: Dokuz Eylul University /ID# 147442
city: Samsun
country: Turkey
facility: Ondokuz mayis University Facul /ID# 147326
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hosp NHS /ID# 149581
city: Bristol
country: United Kingdom
facility: Univ Hosp Bristol NHS Foundati /ID# 147647
city: Southampton
country: United Kingdom
facility: Southampton General Hospital /ID# 147646
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Tr /ID# 147945
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: