Open-label Phase 3 BTK Inhibitor Ibrutinib vs Chlorambucil Patients 65 Years or Older With Treatment-naive CLL or SLL
NCT ID: NCT01722487
Last Updated: 2017-11-30
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
269 participants
INTERVENTIONAL
2013-03-31
2015-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Eligible patients will be randomized in a 1:1 ratio to Treatment Arm A or B:
* Treatment Arm A: Oral Chlorambucil 0.5 mg/kg on Days 1 and 15 of each 28-day cycle; the dose can be increased, if well tolerated, in increments of 0.1 mg/kg on Day 1 of each cycle to a maximum of 0.8 mg/kg; patients receive a minimum of 3 and a maximum of 12 cycles, in the absence of progressive disease or unacceptable toxicity.
* Treatment Arm B: Oral Ibrutinib 420 mg/day Randomization will be stratified on Eastern Cooperative Oncology Group (ECOG) performance status (0,1 versus 2); presence of advanced Rai stage (yes/no), advanced being defined as Stages 3-4; and geographic region: US versus non-US.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Ibrutinib
Ibrutinib will be supplied as hard gelatin 140-mg capsules for oral (PO) administration. Ibrutinib 420 mg (3 x 140-mg capsules) is administered orally once daily. The first dose will be delivered in the clinic on Day 1, after which subsequent dosing is typically on an outpatient basis. Ibrutinib will be dispensed to patients in bottles at each visit.
Ibrutinib
Ibrutinib will be supplied as hard gelatin 140-mg capsules for oral (PO) administration. Ibrutinib 420 mg (3 x 140-mg capsules) is administered orally once daily. The first dose will be delivered in the clinic on Day 1, after which subsequent dosing is typically on an outpatient basis. Ibrutinib will be dispensed to patients in bottles at each visit.
Chlorambucil
Chlorambucil will be supplied as 2-mg tablets for PO administration. Chlorambucil is administered orally on Days 1 and 15 of each 28-day cycle.The starting dosage (Cycle 1) is 0.5 mg/kg. If well tolerated, the Chlorambucil dose can be increased starting at Cycle 2, with increments of 0.1 mg/kg on Day 1 of each cycle to a maximum of 0.8 mg/kg.
Chlorambucil
Chlorambucil will be supplied as 2-mg tablets for PO administration. Chlorambucil is administered orally on Days 1 and 15 of each 28-day cycle. The starting dosage (Cycle 1) is 0.5 mg/kg. If well tolerated, the Chlorambucil dose can be increased starting at Cycle 2, with increments of 0.1 mg/kg on Day 1 of each cycle to a maximum of 0.8 mg/kg.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ibrutinib
Ibrutinib will be supplied as hard gelatin 140-mg capsules for oral (PO) administration. Ibrutinib 420 mg (3 x 140-mg capsules) is administered orally once daily. The first dose will be delivered in the clinic on Day 1, after which subsequent dosing is typically on an outpatient basis. Ibrutinib will be dispensed to patients in bottles at each visit.
Chlorambucil
Chlorambucil will be supplied as 2-mg tablets for PO administration. Chlorambucil is administered orally on Days 1 and 15 of each 28-day cycle. The starting dosage (Cycle 1) is 0.5 mg/kg. If well tolerated, the Chlorambucil dose can be increased starting at Cycle 2, with increments of 0.1 mg/kg on Day 1 of each cycle to a maximum of 0.8 mg/kg.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* creatinine clearance \< 70 mL/min using the Cockcroft-Gault equation
* platelet count \< 100,000/μL or hemoglobin \< 10 g/dL
* clinically apparent autoimmune cytopenia (autoimmune hemolytic anemia or immune thrombocytopenia)
* ECOG performance score = 1 or 2
2. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria (Hallek 2008)
3. Active disease meeting at least 1 of the following IWCLL criteria (Hallek 2008) for requiring treatment:
* Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia Massive, progressive, or symptomatic splenomegaly
* Massive nodes or progressive or symptomatic lymphadenopathy
* Progressive lymphocytosis
* Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly responsive to corticosteroids or standard therapy
* Constitutional symptoms
4. Measurable nodal disease by computed tomography (CT)
5. ECOG performance status of 0-2
6. Life expectancy \> 4 months from randomization
7. Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1,000/μL (independent of growth factor support for at least 7 days prior to screening) and platelet count ≥ 50,000/μL (independent of transfusion and growth factor support for at least 7 days prior to screening)
8. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN
9. Adequate renal function, defined as estimated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
10. Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study
11. Willingness of male patients, if sexually active with a female of childbearing potential, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug
12. Ability to provide written informed consent and to understand and comply with the requirements of the study
Exclusion Criteria
2. History or current evidence of Richter's transformation or prolymphocytic leukemia
3. Documentation of deletion of the short arm of chromosome 17: del(17p13.1) in more than 20% of cells examined on any pretreatment fluorescence in situ hybridization (FISH) or cytogenetic evaluation
4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura
5. Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL/SLL
6. Received any immunotherapy, vaccine, or investigational drug within 4 weeks prior to randomization
7. Corticosteroid use within 1 week prior to first dose of study drug, with the exception of inhaled, topical, or other local administrations. Patients requiring systemic steroids at daily doses \> 20 mg prednisone (or corticosteroid equivalent, see Appendix N), or those who are administered steroids for leukemia control or white blood cell (WBC)-count-lowering are excluded.
8. Major surgery within 4 weeks prior to randomization
9. History of prior malignancy, with the exception of the following:
* malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
* adequately treated nonmelanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
* adequately treated cervical carcinoma in situ without current evidence of disease
10. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 6 months prior to randomization
11. Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function
12. Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics
13. Known history of infection with human immunodeficiency virus (HIV)
14. Serologic status reflecting active hepatitis B or C infection
15. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
16. Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk
17. Requirement for anticoagulation with warfarin
18. Requirement for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor
65 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Janssen Research & Development, LLC
INDUSTRY
Pharmacyclics LLC.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Lori Styles, MD
Role: STUDY_DIRECTOR
Pharmacyclics LLC.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Site Reference ID/Investigator #529
Gdansk, , Poland
Site Reference ID/Investigator #531
Lodz, , Poland
Site Reference ID/Investigator #707
Ryazan, , Russia
Site Reference ID/Investigator #304
Yaroslavl, , Russia
Site Reference ID/Investigator #047
Duarte, California, United States
Site Reference ID/Investigator #408
La Jolla, California, United States
Site Reference ID/Investigator #720
Santa Rosa, California, United States
Site Reference ID/Investigator #038
Stanford, California, United States
Site Reference ID/Investigator #125
Atlanta, Georgia, United States
Site Reference ID/Investigator #126
Chicago, Illinois, United States
Site Reference ID/Investigator #071
Louisville, Kentucky, United States
Site Reference ID/Investigator #307
Worcester, Massachusetts, United States
Site Reference ID/Investigator #387
Ann Arbor, Michigan, United States
Site Reference ID/Investigator #221
St Louis, Missouri, United States
Site Reference ID/Investigator #712
Las Vegas, Nevada, United States
Site Reference ID/Investigator #350
New Hyde Park, New York, United States
Site Reference ID/Investigator #127
Rochester, New York, United States
Site Reference ID/Investigator #656
Goldsboro, North Carolina, United States
Site Reference ID/Investigator #734
Columbus, Ohio, United States
Site Reference ID/Investigator #677
Portland, Oregon, United States
Site Reference ID/Investigator #050
Pittsburgh, Pennsylvania, United States
Site Reference ID/Investigator #032
Houston, Texas, United States
Site Reference ID/Investigator #381
Laredo, Texas, United States
Site Reference ID/Investigator #653
San Antonio, Texas, United States
Site Reference ID/Investigator #404
Seattle, Washington, United States
Site Reference ID/Investigator #731
Walla Walla, Washington, United States
Site Reference ID/Investigator #654
Kogarah, New South Wales, Australia
Site Reference ID/Investigator #503
Woolloongabba, Queensland, Australia
Site Reference ID/Investigator #163
Bedford Park, South Australia, Australia
Site Reference ID/Investigator #555
Hobart, Tasmania, Australia
Site Reference ID/Investigator #193
Box Hill, Victoria, Australia
Site Reference ID/Investigator #556
Clayton, Victoria, Australia
Site Reference ID/Investigator #501
Fitzroy, Victoria, Australia
Site Reference ID/Investigator #715
Frankston, Victoria, Australia
Site Reference ID/Investigator #558
Geelong, Victoria, Australia
Site Reference ID/Investigator #170
Heidelberg, Victoria, Australia
Site Reference ID/Investigator #164
Brussels, Brussells, Belgium
Site Reference ID/Investigator #727
Yvoir, Namur, Belgium
Site Reference ID/Investigator #560
Ghent, Oost-Vlaanderen, Belgium
Site Reference ID/Investigator #559
Leuven, Vlaams Brabant, Belgium
Site Reference ID/Investigator #628
Bruges, West-Vlaanderen, Belgium
Site Reference ID/Investigator #561
Antwerp, , Belgium
Site Reference ID/Investigator #184
Brussells, , Belgium
Site Reference ID/Investigator #157
Calgary, Alberta, Canada
Site Reference ID/Investigator #018
Edmonton, Alberta, Canada
Site Reference ID/Investigator #159
Ottawa, Ontario, Canada
Site Reference ID/Investigator #674
Guangzhou, Guangdong, China
Site Reference ID/Investigator #671
Nanjing, Jiangsu, China
Site Reference ID/Investigator #675
Hangzhou, Zhejiang, China
Site Reference ID/Investigator #670
Beijing, , China
Site Reference ID/Investigator #673
Beijing, , China
Site Reference ID/Investigator #564
Hradec Králové, Královéhradecký kraj, Czechia
Site Reference ID/Investigator #562
Brno, , Czechia
Site Reference ID/Investigator #566
Plzen-Lochotin, , Czechia
Site Reference ID/Investigator #572
Dublin, , Ireland
Site Reference ID/Investigator #570
Dublin, , Ireland
Site Reference ID/Investigator #571
Galway, , Ireland
Site Reference ID/Investigator #573
Haifa, , Israel
Site Reference ID/Investigator #576
Haifa, , Israel
Site Reference ID/Investigator #577
Jerusalem, , Israel
Site Reference ID/Investigator #578
Nahariya, , Israel
Site Reference ID/Investigator #575
Petah Tikva, , Israel
Site Reference ID/Investigator #574
Ramat Gan, , Israel
Site Reference ID/Investigator #583
Rome, Lazio, Italy
Site Reference ID/Investigator #522
Rozzano, Milano, Italy
Site Reference ID/Investigator #582
Novara, Piedmont, Italy
Site Reference ID/Investigator #527
Padua, Veneto, Italy
Site Reference ID/Investigator #580
Bologna, , Italy
Site Reference ID/Investigator #584
Milan, , Italy
Site Reference ID/Investigator #523
Milan, , Italy
Site Reference ID/Investigator #581
Milan, , Italy
Site Reference ID/Investigator #524
Modena, , Italy
Site Reference ID/Investigator #589
Christchurch, Canterbury, New Zealand
Site Reference ID/Investigator #586
Hamilton, Waikato Region, New Zealand
Site Reference ID/Investigator #663
Auckland, , New Zealand
Site Reference ID/Investigator #588
Auckland, , New Zealand
Site Reference ID/Investigator #587
Wellington, , New Zealand
Site Reference ID/Investigator #590
Lublin, Lublin Voivodeship, Poland
Site Reference ID/Investigator #592
Brzozowie, Podkarpackie Voivodeship, Poland
Site Reference ID/Investigator #591
Chorzów, , Poland
Site Reference ID/Investigator #536
Majadahonda, Madrid, Spain
Site Reference ID/Investigator #534
Barcelona, , Spain
Site Reference ID/Investigator #533
Barcelona, , Spain
Site Reference ID/Investigator #535
Barcelona, , Spain
Site Reference ID/Investigator #604
Barcelona, , Spain
Site Reference ID/Investigator #537
Madrid, , Spain
Site Reference ID/Investigator #608
Ankara, , Turkey (Türkiye)
Site Reference ID/Investigator #606
Ankara, , Turkey (Türkiye)
Site Reference ID/Investigator #599
Istanbul, , Turkey (Türkiye)
Site Reference ID/Investigator #714
Izmir, , Turkey (Türkiye)
Site Reference ID/Investigator #601
Izmir, , Turkey (Türkiye)
Site Reference ID/Investigator #602
Kayseri, , Turkey (Türkiye)
Site Reference ID/Investigator #598
Simferopol, Autonomous Republic of Crimea, Ukraine
Site Reference ID/Investigator #597
Cherkasy, Cherkasy Oblast, Ukraine
Site Reference ID/Investigator #594
Dnipropetrovsk, Dnipropetrovsk Oblast, Ukraine
Site Reference ID/Investigator #725
Kharkiv, Kharkivs’ka Oblast’, Ukraine
Site Reference ID/Investigator #596
Lviv, Lviv Oblast, Ukraine
Site Reference ID/Investigator #595
Vinnytsia, Vinnytsia Oblast, Ukraine
Site Reference ID/Investigator #724
Zhytomyr, Zhytomyr Oblast, Ukraine
Site Reference ID/Investigator #551
Bournemouth, Dorset, United Kingdom
Site Reference ID/Investigator #544
London, England, United Kingdom
Site Reference ID/Investigator #668
Oxford, England, United Kingdom
Site Reference ID/Investigator #549
Colchester, Essex, United Kingdom
Site Reference ID/Investigator #607
Cardiff, South Glamergon, United Kingdom
Site Reference ID/Investigator #550
Leeds, Yorkshire, United Kingdom
Site Reference ID/Investigator #721
Birmingham, , United Kingdom
Site Reference ID/Investigator #548
Nottingham, , United Kingdom
Site Reference ID/Investigator #367
Southampton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Abuhelwa AY, Almansour SA, Brown JR, Al-Shamsi HO, Abuhelwa Z, Kharaba Z, Bustanji Y, Semreen MH, Ali S, Alhuraiji A, McKinnon RA, Sorich MJ, Alzoubi KH, Hopkins AM. Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials. Blood Adv. 2025 Jul 22;9(14):3566-3575. doi: 10.1182/bloodadvances.2024015287.
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.
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.
Burger JA, Robak T, Demirkan F, Bairey O, Moreno C, Simpson D, Munir T, Stevens DA, Dai S, Cheung LWK, Kwei K, Lal I, Hsu E, Kipps TJ, Tedeschi A. Up to 6.5 years (median 4 years) of follow-up of first-line ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma and high-risk genomic features: integrated analysis of two phase 3 studies. Leuk Lymphoma. 2022 Jun;63(6):1375-1386. doi: 10.1080/10428194.2021.2020779. Epub 2022 Jan 11.
Allan JN, Shanafelt T, Wiestner A, Moreno C, O'Brien SM, Li J, Krigsfeld G, Dean JP, Ahn IE. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022 Feb;196(4):947-953. doi: 10.1111/bjh.17984. Epub 2021 Dec 5.
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.
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.
Brown JR, Moslehi J, O'Brien S, Ghia P, Hillmen P, Cymbalista F, Shanafelt TD, Fraser G, Rule S, Kipps TJ, Coutre S, Dilhuydy MS, Cramer P, Tedeschi A, Jaeger U, Dreyling M, Byrd JC, Howes A, Todd M, Vermeulen J, James DF, Clow F, Styles L, Valentino R, Wildgust M, Mahler M, Burger JA. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017 Oct;102(10):1796-1805. doi: 10.3324/haematol.2017.171041. Epub 2017 Jul 27.
Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ; RESONATE-2 Investigators. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015 Dec 17;373(25):2425-37. doi: 10.1056/NEJMoa1509388. Epub 2015 Dec 6.
Related Links
Access external resources that provide additional context or updates about the study.
www.pharmacyclics.com
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2012-003967-23
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PCYC-1115-CA
Identifier Type: -
Identifier Source: org_study_id