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

Phase 3
Completed
Conditions
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions
Registration Number
NCT01724346
Lead Sponsor
Pharmacyclics LLC.
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)

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
232
Inclusion Criteria
  1. Randomized in the parent study, PCYC-1115-CA
  2. Informed consent for Study PCYC-1116-CA
  3. IRC-confirmed PD in the parent study PCYC-1115-CA or closure of the parent study
Exclusion Criteria
  1. Disease progression involving the central nervous system (CNS) or transformation to another histology
  2. Intervening chemotherapy, immunotherapy, or investigational agent specifically to treat CLL if administered before date of IRC confirmed progressive disease
  3. In the 4 weeks before dosing: radiation therapy, major surgery, or receipt of an investigational drug
  4. Requirement for treatment with a strong CYP3A inhibitor
  5. Uncontrolled systemic infection or requirement for IV antibiotics
  6. Noncompliance on the parent study(PCYC-1115-CA)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
ChlorambucilIbrutinibParticipants 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).
IbrutinibNext-line ibrutinibParticipants 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.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) Based on Investigator AssessmentMedian overall follow-up of 82.7 months

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.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival After Initiation of Subsequent Anticancer Therapy (PFS2)Median overall follow-up of 82.7 months

PFS2 is defined as the time from the date of randomization to the earliest occurrence of the following three types of events:

* PD per investigator response assessment after initiation of the first subsequent anti-cancer therapy

* Initiation of second subsequent anti-cancer therapy

* Death due to any cause, regardless of administration of subsequent anticancer therapy.

Kaplan-Meier landmark estimate of the PFS2 rate at 60 months (that is, the estimated percentage of participants with PFS2 at Month 60) is presented.

Overall Survival (OS)Median overall follow-up of 82.7 months

OS is defined as the time from randomization to death due to any cause. Kaplan-Meier landmark estimate of the OS rate at 60 months (that is, the estimated percentage of participants with OS at Month 60) is presented.

Time to Next Treatment (TTNT)Median overall follow-up of 82.7 months

Time from randomization to initiation of any subsequent treatment for chronic lymphocytic leukemia (CLL).

Overall Response Rate (ORR)Median overall follow-up of 82.7 months

ORR is defined as the percentage of participants who achieve complete response (CR), complete response with an incomplete marrow recovery (CRi), nodular partial response (nPR), or partial response (PR), as determined by the investigator at or prior to initiation of subsequent antineoplastic therapy according to the International Workshop on CLL (iwCLL) 2008 criteria with the 2012 iwCLL modification stating that treatment-related lymphocytosis in the setting of improvement in other parameters was not considered as PD and the 2013 iwCLL clarification of criteria for a partial response to therapy.

Rate of Minimal Residual Disease (MRD) NegativityMedian overall follow-up of 82.7 months

Percentage of participants who achieved MRD-negative response defined as \< 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate and/or peripheral blood sample per central laboratory at or prior to initiation of subsequent antineoplastic therapy.

Duration of Response (DOR)Median overall follow-up of 82.7 months

DOR will be calculated for the participants achieving a protocol-defined response (Halleck 2008; CR, CRi, nPR, PR) per investigator assessment and is defined as time from the date of initial response including PR with lymphocytosis to the date of disease progression or the date of death from any cause, whichever occurs first.

Trial Locations

Locations (88)

Hospital Universitario HM Sanchinarro /ID# 1116-0537

🇪🇸

Madrid, Spain

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

🇪🇸

Barcelona, Spain

Gazi Universitesi Tip Fakultes /ID# 1116-0608

🇹🇷

Yenimahalle, Ankara, Turkey

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

🇹🇷

Ankara, Turkey

City of Hope /ID# 1116-0047

🇺🇸

Duarte, California, United States

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

🇺🇸

La Jolla, California, United States

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

🇺🇸

Stanford, California, United States

University of Chicago /ID# 1116-0126

🇺🇸

Chicago, Illinois, United States

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

🇺🇸

Louisville, Kentucky, United States

Comprehensive Cancer Centers of Nevada /ID# 1116-0712

🇺🇸

Henderson, Louisiana, United States

University of Massachusetts - Worcester /ID# 1116-0307

🇺🇸

Worcester, Massachusetts, United States

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

🇺🇸

Saint Louis, Missouri, United States

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

🇺🇸

New Hyde Park, New York, United States

University of Rochester Medical Center /ID# 1116-0127

🇺🇸

Rochester, New York, United States

Southeastern Medical Oncology Center /ID# 1116-0656

🇺🇸

Goldsboro, North Carolina, United States

Kaiser Permanente - Northwest /ID# 1116-0677

🇺🇸

Portland, Oregon, United States

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

🇺🇸

Pittsburgh, Pennsylvania, United States

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

🇺🇸

Houston, Texas, United States

Oncology of San Antonio /ID# 1116-0653

🇺🇸

San Antonio, Texas, United States

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

🇺🇸

Walla Walla, Washington, United States

St George Hospital /ID# 1116-0654

🇦🇺

Kogarah, New South Wales, Australia

Princess Alexandra Hospital /ID# 1116-0503

🇦🇺

Woolloongabba, Queensland, Australia

Flinders Medical Centre /ID# 1116-0163

🇦🇺

Bedford, Park, South Australia, Australia

Royal Hobart /ID# 1116-0555

🇦🇺

Hobart, Tasmania, Australia

Box Hill Hospital /ID# 1116-0193

🇦🇺

Box Hill, Victoria, Australia

Monash Medical Centre /ID# 1116-0556

🇦🇺

Clayton, Victoria, Australia

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

🇦🇺

Fitzroy Melbourne, Victoria, Australia

Austin Health /ID# 1116-0170

🇦🇺

Heidelberg, Victoria, Australia

ZNA Cadix /ID# 1116-0561

🇧🇪

Antwerp, Antwerpen, Belgium

UCL Saint-Luc /ID# 1116-0164

🇧🇪

Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium

UZ Gent /ID# 1116-0560

🇧🇪

Gent, Oost-Vlaanderen, Belgium

Universitair Ziekenhuis Leuven /ID# 1116-0559

🇧🇪

Leuven, Vlaams-Brabant, Belgium

Tom Baker Cancer Centre /ID# 1116-0157

🇨🇦

Calgary, Alberta, Canada

Cross Cancer Institute /ID# 1116-0018

🇨🇦

Edmonton, Alberta, Canada

Beijing Cancer Hospital /ID# 1116-0670

🇨🇳

Beijing, Beijing, China

Peking University Third Hospital /ID# 1116-0673

🇨🇳

Beijing, Beijing, China

Jiangsu Province Hospital /ID# 1116-0671

🇨🇳

Nanjing, Jiangsu, China

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

🇨🇳

Hangzhou, Zhejiang, China

Fakultni nemocnice Brno /ID# 1116-0562

🇨🇿

Brno, Czechia

Fakultni nemocnice Hradec Kralove /ID# 1116-0564

🇨🇿

Hradec Kralove, Czechia

Fakultni nemocnice Plzen /ID# 1116-0566

🇨🇿

Plzen, Czechia

St James Hospital /ID# 1116-0570

🇮🇪

Dublin 8, Dublin, Ireland

University Hospital Galway /ID# 1116-0571

🇮🇪

Galway, Ireland

Rambam Health Care Campus /ID# 1116-0576

🇮🇱

Haifa, H_efa, Israel

Bnai Zion Medical Center /ID# 1116-0573

🇮🇱

Haifa, H_efa, Israel

Rabin Medical Center /ID# 1116-0575

🇮🇱

Haifa, H_efa, Israel

Galilee Medical Center /ID# 1116-0578

🇮🇱

Nahariya, HaTsafon, Israel

Shaare Zedek Medical Center /ID# 1116-0577

🇮🇱

Jerusalem, Yerushalayim, Israel

Tel Aviv Sourasky Medical Center /ID# 1116-0856

🇮🇱

Tel Aviv-Yafo, Israel

Institute of Hematology Seràgnoli /ID# 1116-0580

🇮🇹

Bologna, Emilia-Romagna, Italy

Ospedale San Raffaele IRCCS /ID# 1116-0523

🇮🇹

Milan, Milano, Italy

ASST Grande Ospedale Metropolitano Niguarda /ID# 1116-0581

🇮🇹

Milan, Milano, Italy

Università La Sapienza /ID# 1116-0583

🇮🇹

Rome, Roma, Italy

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

🇮🇹

Milan, Italy

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

🇮🇹

Modena, Italy

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

🇮🇹

Novara, Italy

Universita degli Studi di Padova /ID# 1116-0527

🇮🇹

Padova, Italy

Policlinico Universitario A Gemelli /ID# 1116-0891

🇮🇹

Rome, Italy

Auckland City Hospital /ID# 1116-0588

🇳🇿

Grafton, Auckland, New Zealand

North Shore Hospital /ID# 1116-0663

🇳🇿

Takapuna, Auckland, New Zealand

Haematology Waikato Hospital /ID# 1116-0586

🇳🇿

Hamilton, Waikato, New Zealand

Wellington Blood and Cancer Centre /ID# 1116-0587

🇳🇿

Wellington South, Wellington, New Zealand

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

🇳🇿

Christchurch, New Zealand

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

🇵🇱

Warszawa, Mazowieckie, Poland

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

🇵🇱

Brzozow, Podkarpackie, Poland

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

🇵🇱

Gdańsk, Pomorskie, Poland

Samodzielny Publiczny Zaklad Opieki Zdrowotnej /ID# 1116-0591

🇵🇱

Chorzow, Slaskie, Poland

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

🇵🇱

Lodz, Poland

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

🇷🇺

Ryazan, Ryazanskaya Oblast, Russian Federation

Hospital Duran i Reynals /ID# 1116-0604

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

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

🇪🇸

Majadahonda, Madrid, Spain

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

🇪🇸

Barcelona, Spain

Hospital Clinic de Barcelona /ID# 1116-0533

🇪🇸

Barcelona, Spain

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

🇹🇷

Izmir, Turkey

Dokuz Eylul University Medical Faculty /ID# 1116-0601

🇹🇷

Izmir, Turkey

Erciyes Universiitesi Tip Fakultesi /ID# 1116-0602

🇹🇷

Kayseri, Turkey

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

🇺🇦

Vinnytsia, Vinnytska Oblast, Ukraine

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

🇺🇦

Cherkasy, Ukraine

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

🇺🇦

Dnipro, Ukraine

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

🇺🇦

Lviv, Ukraine

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

🇬🇧

Poole, Dorset, United Kingdom

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

🇬🇧

Southampton, Hampshire, United Kingdom

Nottingham University Hospitals NHS Trust /ID# 1116-0548

🇬🇧

Nottingham, Nottinghamshire, United Kingdom

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

🇬🇧

Oxford, Oxfordshire, United Kingdom

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

🇬🇧

Cardiff, Wales, United Kingdom

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

🇬🇧

Colchester, United Kingdom

Leeds Teaching Hospitals NHS Trust /ID# 1116-0550

🇬🇧

Leeds, United Kingdom

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

🇬🇧

London, United Kingdom

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