Open-label Extension Study in Patients 65 Years or Older With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT01724346 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: PCYC-1116-CA2012-003968-44
• Study Type: interventional
• Target: 269
• Locations: 16 countries
• Sites: 88

Brief Summary

An Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

CLL; SLL

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Based on Investigator Assessment

  PFS is defined as the time from the date of randomization to the date of disease progression determined by the investigator or date of death from any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to disease progression (PD) or death. Estimated by Kaplan-Meier method.

  Median overall follow-up of 82.7 months

Secondary Outcomes (6)

• Progression Free Survival After Initiation of Subsequent Anticancer Therapy (PFS2)

  Median overall follow-up of 82.7 months

• Overall Survival (OS)

  Median overall follow-up of 82.7 months

• Time to Next Treatment (TTNT)

  Median overall follow-up of 82.7 months

• Overall Response Rate (ORR)

  Median overall follow-up of 82.7 months

• Rate of Minimal Residual Disease (MRD) Negativity

  Median overall follow-up of 82.7 months

Study Arms (2)

Chlorambucil

EXPERIMENTAL

Participants who received chlorambucil 0.5 mg/kg (to maximum 0.8 mg/kg) Days 1 and 15 of 28-day cycle up to 12 cycles in Study 1115. In Study 1116, participants had the option to crossover to next-line ibrutinib 420 mg/day after disease progression (PD).

Drug: Ibrutinib

Ibrutinib

EXPERIMENTAL

Participants who received ibrutinib 420 mg daily in Study 1115 received ibrutinib orally once daily. Participants continuing in first-line ibrutinib therapy entered Study 1116 at the ibrutinib dose tolerated in Study 1115.

Drug: Next-line ibrutinib

Interventions

Ibrutinib DRUG

Ibrutinib 420 mg (3 x 140-mg capsules) is administered orally once daily

Also known as: PCI-32765

Chlorambucil

Next-line ibrutinib DRUG

Ibrutinib 420 mg (3 x 140-mg capsules) is administered orally once daily

Also known as: PCI-32765

Ibrutinib

Eligibility Criteria

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

You may qualify if:

• Randomized in the parent study, PCYC-1115-CA
• Informed consent for Study PCYC-1116-CA
• Independent review committee (IRC)-confirmed disease progression (PD) in the parent study PCYC-1115-CA or closure of the parent study

You may not qualify if:

• Disease progression involving the central nervous system (CNS) or transformation to another histology
• Intervening chemotherapy, immunotherapy, or investigational agent specifically to treat CLL if administered before date of IRC confirmed progressive disease
• In the 4 weeks before dosing: radiation therapy, major surgery, or receipt of an investigational drug
• Requirement for treatment with a strong CYP3A inhibitor
• Uncontrolled systemic infection or requirement for IV antibiotics
• Noncompliance on the parent study(PCYC-1115-CA)

Sponsors & Collaborators

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

Study Sites (88)

City of Hope /ID# 1116-0047

Duarte, California, 91010, United States

Location

Moores Cancer Center at UC San Diego /ID# 1116-0408

La Jolla, California, 92093, United States

Location

Stanford University/Stanford Cancer Center, Campus Drive /ID# 1116-0038

Stanford, California, 94305, United States

Location

University of Chicago /ID# 1116-0126

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute - St Matthews /ID# 1116-0071

Louisville, Kentucky, 40207, United States

Location

Comprehensive Cancer Centers of Nevada /ID# 1116-0712

Henderson, Louisiana, 89052, United States

Location

University of Massachusetts - Worcester /ID# 1116-0307

Worcester, Massachusetts, 01655, United States

Location

Washington University-School of Medicine /ID# 1116-0221

St Louis, Missouri, 63110, United States

Location

Northwell Health/Long Island Jewish Hospital /ID# 1116-0350

New Hyde Park, New York, 11042, United States

Location

University of Rochester Medical Center /ID# 1116-0127

Rochester, New York, 14642-0001, United States

Location

Southeastern Medical Oncology Center /ID# 1116-0656

Goldsboro, North Carolina, 27534, United States

Location

Kaiser Permanente - Northwest /ID# 1116-0677

Portland, Oregon, 97227, United States

Location

University of Pittsburgh - UPMC (Hillman Cancer Center) /ID# 1116-0050

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas MD Anderson Cancer Center /ID# 1116-0032

Houston, Texas, 77030, United States

Location

Oncology of San Antonio /ID# 1116-0653

San Antonio, Texas, 78240, United States

Location

Providence St. Mary Regional Cancer Center /ID# 1116-0731

Walla Walla, Washington, 99362, United States

Location

St George Hospital /ID# 1116-0654

Kogarah, New South Wales, 2217, Australia

Location

Princess Alexandra Hospital /ID# 1116-0503

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre /ID# 1116-0163

Bedford Park, South Australia, 5042, Australia

Location

Royal Hobart /ID# 1116-0555

Hobart, Tasmania, 7000, Australia

Location

Box Hill Hospital /ID# 1116-0193

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre /ID# 1116-0556

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne /ID# 1116-0501

Fitzroy Melbourne, Victoria, 3065, Australia

Location

Austin Health /ID# 1116-0170

Heidelberg, Victoria, 3084, Australia

Location

ZNA Cadix /ID# 1116-0561

Antwerp, Antwerpen, 2030, Belgium

Location

UCL Saint-Luc /ID# 1116-0164

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

Location

UZ Gent /ID# 1116-0560

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Universitair Ziekenhuis Leuven /ID# 1116-0559

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Tom Baker Cancer Centre /ID# 1116-0157

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute /ID# 1116-0018

Edmonton, Alberta, T6G 1Z2, Canada

Location

Beijing Cancer Hospital /ID# 1116-0670

Beijing, Beijing Municipality, 100142, China

Location

Peking University Third Hospital /ID# 1116-0673

Beijing, Beijing Municipality, 100191, China

Location

Jiangsu Province Hospital /ID# 1116-0671

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 1116-0675

Hangzhou, Zhejiang, 310003, China

Location

Fakultni nemocnice Brno /ID# 1116-0562

Brno, 613 00, Czechia

Location

Fakultni nemocnice Hradec Kralove /ID# 1116-0564

Hradec Králové, 500 05, Czechia

Location

Fakultni nemocnice Plzen /ID# 1116-0566

Pilsen, 305 99, Czechia

Location

St James Hospital /ID# 1116-0570

Dublin, Dublin, D08 NHY1, Ireland

Location

University Hospital Galway /ID# 1116-0571

Galway, H91 YR71, Ireland

Location

Rambam Health Care Campus /ID# 1116-0576

Haifa, H_efa, 3109601, Israel

Location

Bnai Zion Medical Center /ID# 1116-0573

Haifa, H_efa, 3339419, Israel

Location

Rabin Medical Center /ID# 1116-0575

Haifa, H_efa, 4941492, Israel

Location

Shaare Zedek Medical Center /ID# 1116-0577

Jerusalem, Jerusalem, 91031, Israel

Location

Galilee Medical Center /ID# 1116-0578

Nahariya, Northern District, 2210001, Israel

Location

Tel Aviv Sourasky Medical Center /ID# 1116-0856

Tel Aviv, 6423906, Israel

Location

Institute of Hematology Seràgnoli /ID# 1116-0580

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale San Raffaele IRCCS /ID# 1116-0523

Milan, Milano, 20132, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda /ID# 1116-0581

Milan, Milano, 20162, Italy

Location

Università La Sapienza /ID# 1116-0583

Rome, Roma, 00161, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 1116-0584

Milan, 20122, Italy

Location

Azienda Ospedaliero-Universitaria di Modena /ID# 1116-0524

Modena, 41124, Italy

Location

Azienda Ospedaliero Universitaria Maggiore della Carita di Novara /ID# 1116-0582

Novara, 28100, Italy

Location

Universita degli Studi di Padova /ID# 1116-0527

Padua, 35128, Italy

Location

Policlinico Universitario A Gemelli /ID# 1116-0891

Rome, 00168, Italy

Location

Auckland City Hospital /ID# 1116-0588

Grafton, Auckland, 1023, New Zealand

Location

North Shore Hospital /ID# 1116-0663

Takapuna, Auckland, 0622, New Zealand

Location

Haematology Waikato Hospital /ID# 1116-0586

Hamilton, Waikato Region, 3204, New Zealand

Location

Wellington Blood and Cancer Centre /ID# 1116-0587

Wellington South, Wellington Region, 6021, New Zealand

Location

Canterbury Health Labs Canterbury Disrict Health Board /ID# 1116-0589

Christchurch, 8011, New Zealand

Location

MTZ Clinical Research Sp. z o.o. /ID# 1116-0363

Warsaw, Masovian Voivodeship, 02-172, Poland

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. /ID# 1116-0592

Brzozów, Podkarpackie Voivodeship, 36-200, Poland

Location

Samodzielny Publiczny Szpital Klinczny Nr-1- Akademickie Cenrum Klinic /ID# 1116-0529

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej /ID# 1116-0591

Chorzów, Silesian Voivodeship, 41-500, Poland

Location

Medical Univ. of Lodz and Copernicus Memorial Hospital /ID# 1116-0531

Lodz, 93-510, Poland

Location

State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 1116-0707

Ryazan, Ryazan Oblast, 390039, Russia

Location

Hospital Duran i Reynals /ID# 1116-0604

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda /ID# 1116-0536

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Vall d'Hebron /ID# 1116-0534

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona /ID# 1116-0533

Barcelona, 08036, Spain

Location

Hospital Santa Creu i Sant Pau /ID# 1116-0535

Barcelona, 08041, Spain

Location

Hospital Universitario HM Sanchinarro /ID# 1116-0537

Madrid, 28050, Spain

Location

Gazi Universitesi Tip Fakultes /ID# 1116-0608

Yenimahalle, Ankara, 06560, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Ibn-i Sina /ID# 1116-0606

Ankara, 06590, Turkey (Türkiye)

Location

Ic Hastaliklari Anabilim Dali/Ege University Medical Faculty /ID# 1116-0714

Izmir, 35040, Turkey (Türkiye)

Location

Dokuz Eylul University Medical Faculty /ID# 1116-0601

Izmir, 35340, Turkey (Türkiye)

Location

Erciyes Universiitesi Tip Fakultesi /ID# 1116-0602

Kayseri, 38039, Turkey (Türkiye)

Location

CNE Vinnytsya Regional Clinical Hospital named after N.I.Pirogov /ID# 1116-0595

Vinnytsia, Vinnytsia Oblast, 21018, Ukraine

Location

Communal Nonprofit Enterprise Cherkasy Regional Oncology Dispensary /ID# 1116-0597

Cherkasy, 18009, Ukraine

Location

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 1116-0594

Dnipro, 49102, Ukraine

Location

SI Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine /ID# 1116-0596

Lviv, 79044, Ukraine

Location

University Hospitals Dorset NHS Foundation Trust /ID# 1116-0551

Poole, Dorset, BH15 2JB, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust /ID# 1116-0367

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Nottingham University Hospitals NHS Trust /ID# 1116-0548

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust /ID# 1116-0668

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Cardiff & Vale University Health Board /ID# 1116-0607

Cardiff, Wales, CF14 4XN, United Kingdom

Location

East Suffolk and North Essex NHS Foundation Trust /ID# 1116-0549

Colchester, CO4 5JL, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust /ID# 1116-0550

Leeds, LS9 7TF, United Kingdom

Location

King's College Hospital NHS Foundation Trust /ID# 1116-0544

London, SE5 9RS, United Kingdom

Location

Related Publications (5)

• Burger JA, Barr PM, Robak T, Owen C, Tedeschi A, Sarma A, Patten PEM, Grosicki S, McCarthy H, Offner F, Szafer-Glusman E, Zhou C, Szoke A, Neumayr L, Dean JP, Ghia P, Kipps TJ. Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL. Blood. 2025 Oct 30;146(18):2168-2176. doi: 10.1182/blood.2024028205.

  PMID: 40737596 DERIVED

• Barr PM, Owen C, Robak T, Tedeschi A, Bairey O, Burger JA, Hillmen P, Dearden C, Grosicki S, McCarthy H, Li JY, Offner F, Moreno C, Jermain M, Zhou C, Hsu E, Szoke A, Kipps TJ, Ghia P. Many People With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Benefit From Ibrutinib Treatment Up To 8 Years: A Plain Language Summary. Future Oncol. 2023 Jan 9. doi: 10.2217/fon-2022-0898. Online ahead of print.

  PMID: 36617990 DERIVED

• Barr PM, Owen C, Robak T, Tedeschi A, Bairey O, Burger JA, Hillmen P, Coutre SE, Dearden C, Grosicki S, McCarthy H, Li JY, Offner F, Moreno C, Zhou C, Hsu E, Szoke A, Kipps TJ, Ghia P. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022 Jun 14;6(11):3440-3450. doi: 10.1182/bloodadvances.2021006434.

  PMID: 35377947 DERIVED

• Coutre SE, Byrd JC, Hillmen P, Barrientos JC, Barr PM, Devereux S, Robak T, Kipps TJ, Schuh A, Moreno C, Furman RR, Burger JA, O'Dwyer M, Ghia P, Valentino R, Chang S, Dean JP, James DF, O'Brien SM. Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood Adv. 2019 Jun 25;3(12):1799-1807. doi: 10.1182/bloodadvances.2018028761.

  PMID: 31196847 DERIVED

• Barr PM, Robak T, Owen C, Tedeschi A, Bairey O, Bartlett NL, Burger JA, Hillmen P, Coutre S, Devereux S, Grosicki S, McCarthy H, Li J, Simpson D, Offner F, Moreno C, Zhou C, Styles L, James D, Kipps TJ, Ghia P. Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2. Haematologica. 2018 Sep;103(9):1502-1510. doi: 10.3324/haematol.2018.192328. Epub 2018 Jun 7.

  PMID: 29880603 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib

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

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: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 9, 2012
• Study Start: December 3, 2013
• Primary Completion: August 18, 2023
• Study Completion: August 18, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

BE (4); RU (1); TU (5); IL (6); AU (8); CN (4); IE (2); UA (4); CA (2); ES (6); GB (8); IT (9); PL (5); US (16); NZ (5); CZ (3)