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)

NCT03462719 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: CR1084282017-004699-7754179060CLL3011
• Study Type: interventional
• Target: 211
• Locations: 14 countries
• Sites: 88

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).

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS: time between date of randomization and date of disease progression, as assessed by IRC, or date of death due to any cause, whichever occurs first, regardless of use of subsequent anti-cancer therapy prior to PD or death using iWCLL2008 criteria : New enlarged lymph nodes \>15 mm, new hepatomegaly or splenomegaly, or other organ infiltrates, bone lesion, ascites or pleural effusion due to CLL; \>=50% increase in longest diameter (LDi) from nadir in existing lymph node (LDi \>15 mm) or \>=50% increase from nadir in sum of diameters of multiple nodes (and at least 1 node with LDi \>15 mm); \>=50% increase from nadir in enlargement of liver/spleen; \>=50% increase from baseline in lymphocyte count (ALC; to \>=5\*10\^9/L); or \>=50% increase from nadir in ALC in \>=2 serial assessments if ALC is \>=30000\*10\^9/L and lymphocyte doubling time is rapid unless considered treatment-related lymphocytosis; new cytopenia attributable to CLL; transformation to more aggressive histology.

  Up to 2 years 10 months

Secondary Outcomes (14)

• Minimal Residual Disease (MRD) Negative Rate

  Up to 2 years 10 months

• Complete Response Rate (CRR)

  Up to 2 years 10 months

• Overall Response Rate (ORR)

  Up to 2 years 10 months

• Overall Survival (OS)

  Up to 4 years 10 months

• Duration of Response (DOR)

  Up to 2 years 10 months

Study Arms (2)

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)

EXPERIMENTAL

Participants will initially receive ibrutinib (420 mg \[milligrams\]/day) for 3 cycles. Venetoclax dose ramp up (from 20 to 400 mg over 5 weeks) will begin at Cycle 4 and the combination of ibrutinib and venetoclax will be given for 12 cycles (each cycle is equivalent to 28 days). Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.

Drug: Ibrutinib; Drug: Venetoclax; Drug: Ibrutinib (as Subsequent Therapy)

Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

ACTIVE COMPARATOR

Participants will receive chlorambucil and obinutuzumab (G-Clb) for 6 cycles. Participants will receive obinutuzumab, 1000 mg intravenously (IV) on Days 1, 8 and 15 of Cycle 1, and on Day 1 of Cycles 2 to 6 and chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight, on Days 1 and 15 of Cycles 1 to 6. Participants who subsequently develop progressive disease may enter to Subsequent Therapy Phase to receive single-agent ibrutinib until disease progression or unacceptable toxicity.

Drug: Chlorambucil; Drug: Obinutuzumab; Drug: Ibrutinib (as Subsequent Therapy)

Interventions

Ibrutinib DRUG

Participants will receive ibrutinib 420 mg orally once daily up to 15 cycles.

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)

Venetoclax DRUG

Participants will receive venetoclax in combination with ibrutinib for a total of 12 cycles, beginning at Cycle 4. For the first 5 weeks of venetoclax treatment, the treatment dose will be ramped up from 20 to 400 mg.

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN)

Chlorambucil DRUG

Participants will receive chlorambucil at a dose of 0.5 mg/kg body weight on Days 1 and 15 of Cycles 1 to 6.

Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

Obinutuzumab DRUG

Participant will receive obinutuzumab 1000 mg intravenously on Days 1, 8, and 15 of Cycle 1, and Day 1 of Cycles 2 to 6.

Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

Ibrutinib (as Subsequent Therapy) DRUG

Participants will receive ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity during the subsequent therapy phase.

Treatment Arm A: Ibrutinib and Venetoclax (I+VEN); Treatment Arm B: Chlorambucil and Obinutuzumab (G-Clb)

Eligibility Criteria

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

You may qualify if:

• 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:
• Cumulative Illness Rating Scale (CIRS) score \> 6
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• Pharmacyclics LLC.: collaborator

Study Sites (88)

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Novant Health

Charlotte, North Carolina, 28204, United States

Location

Institut - Jules Bordet

Anderlecht, 1070, Belgium

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Virga Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

CIUSSS de l Est de l Ile de Montreal Installation Hopital Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Fakultni nemocnice Brno, Interni hematologicka a onkologicka klinika

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni

Pilsen, 323 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie

Prague, 128 08, Czechia

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Aarhus Universitetshospital

Aarhus, 8200, Denmark

Location

Rigshospitalet 1

Copenhagen, 2100, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Roskilde Sygehus

Roskilde, DK- 4000, Denmark

Location

CHU de Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hopital Claude Huriez

Lille, 59000, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Hopital Haut Leveque Service Maladie Du Sang

Pessac, 33604, France

Location

Centre Hospitalier Universitaire de Reims, Hôpital Robert Debré

Reims, 51100, France

Location

Institut Universitaire du Cancer Toulouse Oncopole

Toulouse, 31059, France

Location

CHU Bretonneau

Tours, 37044, France

Location

CHU-Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Carmel Medical Center

Haifa, 34362, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Western Galilee Medical Center

Nahariya, 22100, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Flevoziekenhuis

Almere Stad, 1315RA, Netherlands

Location

OLVG

Amsterdam, 1091AC, Netherlands

Location

Academic Medical Center

Amsterdam, 1105 AZ, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, 2625 AD, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, 3318 AT, Netherlands

Location

Catharinaziekenhuis

Eindhoven, 5623 EJ, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, 2134 TM, Netherlands

Location

Zuyderland Medical Center

Sittard-Geleen, 6162 BG, Netherlands

Location

Antonius hospital

Sneek, 8601 ZK, Netherlands

Location

MC Haaglanden

The Hague, 2512 VA, Netherlands

Location

Elisabeth zkh

Tilburg, 5022 GC, Netherlands

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzów, 41-500, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi

Lodz, 93 510, Poland

Location

Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie

Lublin, 20-081, Poland

Location

Wojewodzki Szpital Specjalistyczny im Janusza Korczaka

Słupsk, 76-200, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02 776, Poland

Location

Moscow Multidisciplinary Scientific and Clinical Center named after S P Botkin

Moscow, 125284, Russia

Location

S.P. Botkin Moscow City Clinical Hospital

Moscow, 125284, Russia

Location

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390039, Russia

Location

St.-Petersburg Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, 193024, Russia

Location

FSBIFederal Centre of Heart, Blood and Endocrinology named after V.A.Almazov MoH of the RF

Saint Petersburg, 197341, Russia

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hosp. Univ. de La Princesa

Madrid, 28006, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Univ. Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Hosp Univ Fund Jimenez Diaz

Madrid, 28040, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hospital Clinico Universitario Salamanca

Salamanca, 37007, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Sunderby Sjukhus Medicinkliniken

Luelå, 97180, Sweden

Location

Karolinska Universitetssjukhuset Solna, Centrum för Hematologi, Stockholm

Stockholm, 171 76, Sweden

Location

Gazi Universitesi Tip Fakultesi

Ankara, 06500, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi

Ankara, 06620, Turkey (Türkiye)

Location

V K V Amerikan Hastanesi

Istanbul, 34365, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi

Izmir, 35340, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi

Samsun, 55280, Turkey (Türkiye)

Location

Birmingham Heartlands Hospital

Birmingham, B9 5ST, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Queen Mary University of London

Charterhouse Square, EC1M 6BQ, United Kingdom

Location

New Victoria Hospital

Glasgow, G42 9LF, United Kingdom

Location

St James's Hospital

Leeds, LS9 7T, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Barking Havering and Redbridge University Hospitals NHS Trust

Romford, RM7 0AG, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• Kater AP, Owen C, Moreno C, Follows G, Munir T, Levin MD, Benjamini O, Janssens A, Osterborg A, Robak T, Simkovic M, Stevens D, Voloshin S, Vorobyev V, Ysebaert L, Qin R, Steele AJ, Schuier N, Baeten K, Caces DB, Niemann CU. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. NEJM Evid. 2022 Jul;1(7):EVIDoa2200006. doi: 10.1056/EVIDoa2200006. Epub 2022 May 13.

  PMID: 38319255 DERIVED

• Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, Janssens A, Levin MD, Robak T, Simkovic M, Voloshin S, Vorobyev V, Yagci M, Ysebaert L, Qi K, Qi Q, Sinet P, Parisi L, Srinivasan S, Schuier N, Baeten K, Howes A, Caces DB, Kater AP. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Dec;24(12):1423-1433. doi: 10.1016/S1470-2045(23)00452-7. Epub 2023 Nov 6.

  PMID: 37944541 DERIVED

• Moreno C, Solman IG, Tam CS, Grigg A, Scarfo L, Kipps TJ, Srinivasan S, Mali RS, Zhou C, Dean JP, Szafer-Glusman E, Choi M. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study. Blood Adv. 2023 Sep 26;7(18):5294-5303. doi: 10.1182/bloodadvances.2023010236.

  PMID: 37315225 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; venetoclax; Chlorambucil; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; 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

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: EXECUTIVE MEDICAL DIRECTOR
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 12, 2018
• Study Start: April 17, 2018
• Primary Completion: February 26, 2021
• Study Completion (Estimated): April 5, 2029
• Last Updated: April 13, 2026
• Results First Posted: March 28, 2022

Record last verified: 2026-04

Locations

US (3); IL (6); PL (5); CA (6); DK (6); CZ (5); NL (11); ES (11); BE (5); SE (2); RU (6); TU (5); FR (9); GB (8)