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

NCT02756611 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: M15-5502015-003667-11
• Study Type: interventional
• Target: 258
• Locations: 21 countries
• Sites: 67

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Oncology; Chronic Lymphocytic Leukemia; 17p Deletion; TP53 Mutation; Relapsed; Refractory; B-Cell receptor inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (10)

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

  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 Response Rate (ORR) - Primary Analysis

  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

  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

  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

  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.

Other Outcomes (9)

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

  From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.

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

  From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.

• Overall Response Rate (ORR) - Final Analysis

  From first dose of study drug until the end of study; overall median time on follow-up was 49.5 months.

Study Arms (1)

Venetoclax

EXPERIMENTAL

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.

Drug: Venetoclax

Interventions

Venetoclax DRUG

Tablets for oral administration

Also known as: ABT-199, VENCLEXTA®

Venetoclax

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie: lead

Study Sites (67)

Norton Cancer Institute /ID# 149788

Louisville, Kentucky, 40202-3700, United States

Location

St. Agnes Cancer Center /ID# 149782

Baltimore, Maryland, 21229, United States

Location

Hackensack Univ Med Ctr /ID# 151574

Hackensack, New Jersey, 07601, United States

Location

Utah Cancer Specialists /ID# 151604

Salt Lake City, Utah, 84106, United States

Location

Cancer Care Northwest /ID# 151605

Spokane, Washington, 99202, United States

Location

West Virginia Univ School Med /ID# 151602

Morgantown, West Virginia, 26506, United States

Location

LKH-Univ. Klinikum Graz /ID# 147547

Graz, 8036, Austria

Location

LKH Salzburg and Paracelsus /ID# 147549

Salzburg, 5020, Austria

Location

Hanusch Krankenhaus der WGKK /ID# 147548

Vienna, 1140, Austria

Location

Cliniques Universitaires Saint Luc /ID# 147388

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

UZ Leuven /ID# 147387

Leuven, 3000, Belgium

Location

BC Cancer Agency /ID# 153091

Vancouver, British Columbia, V5Z 1L3, Canada

Location

Qe Ii Hsc /Id# 147460

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Clinic /ID# 149152

Hamilton, Ontario, L8V 1C3, Canada

Location

Sunnybrook Health Sciences Ctr /ID# 147462

Toronto, Ontario, M4N 3M5, Canada

Location

CHU de Quebec-Universite Laval /ID# 150299

Québec, Quebec, G1R 2J6, Canada

Location

Herlev Hospital /ID# 150183

Herlev, Capital Region, 2730, Denmark

Location

Aarhus University Hospital /ID# 147409

Aarhus N, Central Jutland, 8200, Denmark

Location

Turku University Hospital /ID# 147551

Turku, 20520, Finland

Location

CHU Dupuytren /ID# 147552

Limoges, Franche-Comte, 87042, France

Location

CHU de la miletrie /ID# 147484

Poitiers, Poitou-Charentes, 86021, France

Location

Institut Bergonie /ID# 147482

Bordeaux, 33076, France

Location

CHRU de Brest - Hopital Morvan /ID# 147485

Brest, 29200, France

Location

clinique Sainte Anne /ID# 147556

Strasbourg, 67085, France

Location

Onkologische Schwerpunktpraxis /ID# 147516

Berlin, 10707, Germany

Location

Cent fuer Haematologie und Onk /ID# 147511

Frankfurt, 60389, Germany

Location

OncoResearch Lerchenfeld GmbH /ID# 164044

Hamburg, 22081, Germany

Location

Mannheimer Onkologiepraxis /ID# 147512

Mannheim, 68161, Germany

Location

Staedt. Klinikum Schwabing /ID# 147510

Munich, 80804, Germany

Location

General Hospital of Athens Laiko /ID# 147517

Athens, Attica, 115 27, Greece

Location

G. Papanikolaou Hospital /ID# 147518

Thessaloniki, 57010, Greece

Location

St. James's Hospital /ID# 147519

Dublin, Dublin, D08 E9P6, Ireland

Location

Beaumont Hospital /ID# 147522

Dublin, D09 XR63, Ireland

Location

Tel Aviv Sourasky Medical Ctr /ID# 151624

Tel Aviv, Tel Aviv, 6423906, Israel

Location

Galilee Medical Center /ID# 159971

Nahariya, 22100, Israel

Location

Sheba Medical Center /ID# 147509

Ramat Gan, 5262100, Israel

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

AP Romano Umberto I /ID# 147500

Rome, Lazio, 00161, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 147503

Milan, Lombardy, 20162, Italy

Location

Ospedale San Raffaele IRCCS /ID# 147504

Milan, 20132, Italy

Location

AO Maggiore della Carita /ID# 147499

Novara, 28100, Italy

Location

Academisch Medisch Centrum /ID# 147494

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Albert Schweitzer Ziekenhuis /ID# 147495

Dordrecht, South Holland, 3318 AT, Netherlands

Location

Haukeland University Hospital /ID# 147382

Bergen, Hordaland, 5021, Norway

Location

Rikshospitalet OUS HF /ID# 201812

Oslo, 0450, Norway

Location

IPO Lisboa FG, EPE /ID# 147385

Lisbon, 1099-023, Portugal

Location

IPO Porto FG, EPE /ID# 147389

Porto, 4200-072, Portugal

Location

Puerto Rico Hematology Oncolog /ID# 150003

San Juan, 00959, Puerto Rico

Location

Hospital Santa Creu i Sant Pau /ID# 151230

Barcelona, 08026, Spain

Location

Fundacion Jimenez Diaz /ID# 151231

Madrid, 28040, Spain

Location

Hosp Univ Puerta de Hierro /ID# 147391

Majadahonda, 28222, Spain

Location

Hospital Clinico Univ de Salamanca /ID# 147392

Salamanca, 37007, Spain

Location

Hosp Clin Univ de Valencia /ID# 147396

Valencia, 46010, Spain

Location

Skanes Universitetssjukhus Lund /ID# 147439

Lund, Skåne County, 222 41, Sweden

Location

Akademiska Sjukhuset /ID# 150184

Uppsala, Uppsala County, 751 85, Sweden

Location

Hopitaux Universitaires de Geneve /ID# 147930

Geneva, Canton of Geneva, 1205, Switzerland

Location

University Hospital Zurich /ID# 157910

Zurich, Canton of Zurich, 8006, Switzerland

Location

Ospedale Regional Bellinzona e /ID# 151232

Bellinzona, 6501, Switzerland

Location

Ankara Univ Medical Faculty /ID# 147443

Ankara, 6100, Turkey (Türkiye)

Location

Istanbul University Istanbul Medical Faculty /ID# 156040

Istanbul, 34093, Turkey (Türkiye)

Location

Vehbi Koc vakfi Amerikan Hasta /ID# 147325

Istanbul, 34365, Turkey (Türkiye)

Location

Dokuz Eylul University /ID# 147442

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz mayis University Facul /ID# 147326

Samsun, 55139, Turkey (Türkiye)

Location

Blackpool Teaching Hosp NHS /ID# 149581

Blackpool, FY3 8NR, United Kingdom

Location

Univ Hosp Bristol NHS Foundati /ID# 147647

Bristol, BS2 8EG, United Kingdom

Location

Southampton General Hospital /ID# 147646

Southampton, SO16 6YD, United Kingdom

Location

The Royal Wolverhampton NHS Tr /ID# 147945

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38467131 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms; Chromosome 17 deletion; Recurrence

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: April 29, 2016
• Study Start: June 22, 2016
• Primary Completion: April 10, 2019
• Study Completion: March 11, 2022
• Last Updated: April 10, 2023
• Results First Posted: May 4, 2020

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing, please refer to the link below.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.

Locations

DK (2); NL (2); NO (2); CH (3); PT (2); PR (1); FI (1); IT (5); SE (2); TU (5); ES (5); AU (3); FR (5); DE (5); GR (2); BE (2); IE (2); US (6); GB (4); CA (5); IL (3)