Clinical trial NCT03462719: A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Official title: A Randomized, Open-label, Phase 3 Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Subjects With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Pharmacyclics LLC.
First posted: 2018-03-12
Enrollment: 211
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess progression-free survival (PFS) from treatment with ibrutinib plus venetoclax (I+VEN) compared with obinutuzumab plus chlorambucil (G-Clb) as assessed by an Independent Review Committee (IRC).


Eligibility criteria: Inclusion Criteria:

* Adult participants who are: (a) greater than or equal to (\>=) 65 years old or, (b) 18 to 64 years old and have at least 1 of the following:

  1. Cumulative Illness Rating Scale (CIRS) score \> 6
  2. Creatinine clearance (CrCl) estimated less than (\<) 70 milliliter per minute (mL/min) using Cockcroft-Gault equation
* Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
* Measurable nodal disease (by computed tomography \[CT\]), defined as at least one lymph node \> 1.5 centimeter (cm) in longest diameter
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade less than or equal to (\<=) 2
* Active CLL/SLL requiring treatment per the iwCLL criteria

Exclusion Criteria:

* Prior anti-leukemic therapy for CLL or SLL
* Presence of deletion of the short arm of chromosome 17 (del17p) or known TP53 mutation detected at a threshold of \>10 percent (%) variable allele frequency (VAF)
* Major surgery within 4 weeks of first dose of study treatment
* Known bleeding disorders (example, von Willebrand's disease or hemophilia)
* Central nervous system (CNS) involvement or suspected Richter's syndrome

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years 10 months
Secondary outcomes:
measure: Minimal Residual Disease (MRD) Negative Rate
timeFrame: Up to 2 years 10 months
measure: Complete Response Rate (CRR)
timeFrame: Up to 2 years 10 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years 10 months
measure: Overall Survival (OS)
timeFrame: Up to 4 years 10 months
measure: Duration of Response (DOR)
timeFrame: Up to 2 years 10 months
measure: Time-to-Next Treatment
timeFrame: Up to 2 years 10 months
measure: Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L)
timeFrame: Up to 2 years 10 months
measure: Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30)
timeFrame: Up to 2 years 10 months
measure: Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
timeFrame: Up to 2 years 10 months
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 4 years 10 months
measure: Number of Participants With Abnormal Clinical Laboratory Findings
timeFrame: Up to 4 years 10 months
measure: Percentage of Participants With Sustained Hemoglobin Improvement
timeFrame: Up to 2 years 10 months
measure: Percentage of Participants With Sustained Platelet Improvement
timeFrame: Up to 2 years 10 months
measure: Plasma Concentration of Ibrutinib and Venetoclax
timeFrame: Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Charlotte
country: United States
facility: Novant Health
state: North Carolina
city: Anderlecht
country: Belgium
facility: Institut - Jules Bordet
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Virga Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l Est de l Ile de Montreal Installation Hopital Maisonneuve Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Roskilde
country: Denmark
facility: Roskilde Sygehus
city: Clermont Ferrand
country: France
facility: CHU de Clermont Ferrand
city: Lille
country: France
facility: Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU Montpellier
city: Pessac
country: France
facility: Hopital Haut Leveque Service Maladie Du Sang
city: Reims
country: France
facility: Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Tours Cedex 9
country: France
facility: CHU Bretonneau
city: Vandoeuvre les Nancy
country: France
facility: CHU-Nancy
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: OLVG
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Den Haag
country: Netherlands
facility: MC Haaglanden
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharinaziekenhuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medical Center
city: Sneek
country: Netherlands
facility: Antonius hospital
city: Tilburg
country: Netherlands
facility: Elisabeth zkh
city: Chorzow
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie
city: Slupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im Janusza Korczaka
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Moscow
country: Russian Federation
facility: Moscow Multidisciplinary Scientific and Clinical Center named after S P Botkin
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Hospital
city: Saint Petersburg
country: Russian Federation
facility: FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF
city: St. Petersburg
country: Russian Federation
facility: St.-Petersburg Clinical Research Institute of Hematology and Transfusiology
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario Salamanca
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Luelå
country: Sweden
facility: Sunderby Sjukhus Medicinkliniken
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip FalKultesi
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakültesi Ibn-i Sina Hastanesi
city: Atakum
country: Turkey
facility: Ondokuz Mayis University
city: Istanbul
country: Turkey
facility: V K V Amerikan Hastanesi
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Tip Fakultesi
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Charterhouse Square
country: United Kingdom
facility: Queen Mary University of London
city: Glasgow
country: United Kingdom
facility: New Victoria Hospital
city: Leeds
country: United Kingdom
facility: St James's Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Romford
country: United Kingdom
facility: Barking Havering and Redbridge University Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: