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

NCT ID: NCT02756611

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-22
• Study Completion Date: 2022-03-11

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.

Conditions

Chronic Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Venetoclax

Venetoclax will be administered orally once daily (QD) beginning with a dose-titration phase. The initial venetoclax dose is 20 mg QD. After 1 week of treatment at 20 mg QD, the dose will be escalated to 50 mg QD followed by subsequent increases, each after 1 week, to 100 mg QD, 200 mg QD and the maximum dose of 400 mg QD. Participants may continue to receive venetoclax for up to 2 years provided they continue to tolerate the drug, have no evidence of disease progression (based on investigator's assessment), do not have unacceptable toxicity, and do not meet any of the criteria for discontinuation.

In countries where venetoclax is not commercially available, participants who continue to derive benefit after 2 years of treatment may be able to extend their treatment for up to 2 additional years, plus one additional year until the venetoclax extension study was open, determined on a case by case basis.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Tablets for oral administration

Interventions

Venetoclax

Tablets for oral administration

Intervention Type: DRUG

Other Intervention Names

ABT-199; VENCLEXTA®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

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

UZ Leuven /ID# 147387

Leuven, , Belgium

BC Cancer Agency /ID# 153091

Vancouver, British Columbia, Canada

Qe Ii Hsc /Id# 147460

Halifax, Nova Scotia, Canada

Juravinski Cancer Clinic /ID# 149152

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Ctr /ID# 147462

Toronto, Ontario, Canada

CHU de Quebec-Universite Laval /ID# 150299

Québec, Quebec, Canada

Herlev Hospital /ID# 150183

Herlev, Capital Region, Denmark

Aarhus University Hospital /ID# 147409

Aarhus N, Central Jutland, Denmark

Turku University Hospital /ID# 147551

Turku, , Finland

CHU Dupuytren /ID# 147552

Limoges, Franche-Comte, France

CHU de la miletrie /ID# 147484

Poitiers, Poitou-Charentes, France

Institut Bergonie /ID# 147482

Bordeaux, , France

CHRU de Brest - Hopital Morvan /ID# 147485

Brest, , France

clinique Sainte Anne /ID# 147556

Strasbourg, , France

Onkologische Schwerpunktpraxis /ID# 147516

Berlin, , Germany

Cent fuer Haematologie und Onk /ID# 147511

Frankfurt, , Germany

OncoResearch Lerchenfeld GmbH /ID# 164044

Hamburg, , Germany

Mannheimer Onkologiepraxis /ID# 147512

Mannheim, , Germany

Staedt. Klinikum Schwabing /ID# 147510

Munich, , Germany

General Hospital of Athens Laiko /ID# 147517

Athens, Attica, Greece

G. Papanikolaou Hospital /ID# 147518

Thessaloniki, , Greece

St. James's Hospital /ID# 147519

Dublin, Dublin, Ireland

Beaumont Hospital /ID# 147522

Dublin, , Ireland

Tel Aviv Sourasky Medical Ctr /ID# 151624

Tel Aviv, Tel Aviv, Israel

Galilee Medical Center /ID# 159971

Nahariya, , Israel

Sheba Medical Center /ID# 147509

Ramat Gan, , Israel

A.O.U. Policlinico S.Orsola-Malpighi /ID# 147505

Bologna, Emilia-Romagna, Italy

AP Romano Umberto I /ID# 147500

Rome, Lazio, Italy

ASST Grande Ospedale Metropolitano Niguarda /ID# 147503

Milan, Lombardy, Italy

Ospedale San Raffaele IRCCS /ID# 147504

Milan, , Italy

AO Maggiore della Carita /ID# 147499

Novara, , Italy

Academisch Medisch Centrum /ID# 147494

Amsterdam, North Holland, Netherlands

Albert Schweitzer Ziekenhuis /ID# 147495

Dordrecht, South Holland, Netherlands

Haukeland University Hospital /ID# 147382

Bergen, Hordaland, Norway

Rikshospitalet OUS HF /ID# 201812

Oslo, , Norway

IPO Lisboa FG, EPE /ID# 147385

Lisbon, , Portugal

IPO Porto FG, EPE /ID# 147389

Porto, , Portugal

Puerto Rico Hematology Oncolog /ID# 150003

San Juan, , Puerto Rico

Hospital Santa Creu i Sant Pau /ID# 151230

Barcelona, , Spain

Fundacion Jimenez Diaz /ID# 151231

Madrid, , Spain

Hosp Univ Puerta de Hierro /ID# 147391

Majadahonda, , Spain

Hospital Clinico Univ de Salamanca /ID# 147392

Salamanca, , Spain

Hosp Clin Univ de Valencia /ID# 147396

Valencia, , Spain

Skanes Universitetssjukhus Lund /ID# 147439

Lund, Skåne County, Sweden

Akademiska Sjukhuset /ID# 150184

Uppsala, Uppsala County, Sweden

Hopitaux Universitaires de Geneve /ID# 147930

Geneva, Canton of Geneva, Switzerland

University Hospital Zurich /ID# 157910

Zurich, Canton of Zurich, Switzerland

Ospedale Regional Bellinzona e /ID# 151232

Bellinzona, , Switzerland

Ankara Univ Medical Faculty /ID# 147443

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty /ID# 156040

Istanbul, , Turkey (Türkiye)

Vehbi Koc vakfi Amerikan Hasta /ID# 147325

Istanbul, , Turkey (Türkiye)

Dokuz Eylul University /ID# 147442

Izmir, , Turkey (Türkiye)

Ondokuz mayis University Facul /ID# 147326

Samsun, , Turkey (Türkiye)

Blackpool Teaching Hosp NHS /ID# 149581

Blackpool, , United Kingdom

Univ Hosp Bristol NHS Foundati /ID# 147647

Bristol, , United Kingdom

Southampton General Hospital /ID# 147646

Southampton, , United Kingdom

The Royal Wolverhampton NHS Tr /ID# 147945

Wolverhampton, , United Kingdom

Countries

United States; Austria; Belgium; Canada; Denmark; Finland; France; Germany; Greece; Ireland; Israel; Italy; Netherlands; Norway; Portugal; Puerto Rico; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

Kater AP, Arslan O, Demirkan F, Herishanu Y, Ferhanoglu B, Diaz MG, Leber B, Montillo M, Panayiotidis P, Rossi D, Skarbnik A, Tempescul A, Turgut M, Mellink CH, van der Kevie-Kersemaekers AF, Lanham S, Sale B, Del Rio L, Popovic R, Chyla BJ, Busman T, Komlosi V, Wang X, Sail K, Pena GE, Vizkelety T, Forconi F. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial. Lancet Oncol. 2024 Apr;25(4):463-473. doi: 10.1016/S1470-2045(24)00070-6. Epub 2024 Mar 8.

Reference Type: DERIVED

PMID: 38467131 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-003667-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M15-550

Identifier Type: -

Identifier Source: org_study_id