A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
NCT ID: NCT01578707
Last Updated: 2019-12-18
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
391 participants
INTERVENTIONAL
2012-06-30
2018-10-25
Brief Summary
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Detailed Description
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Patients randomized to the ofatumumab arm may be considered to receive next subsequent therapy with ibrutinib.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Ofatumumab (Arm A)
An anti-CD20 monoclonal antibody
ofatumumab
The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.
Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)
ibrutinib (Arm B)
A Bruton Tyrosine Kinase Inhibitor
ibrutinib
ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity
Interventions
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ofatumumab
The ofatumumab (IV) dosage and schedule is 12 doses administered over 24 weeks or until disease progression, unacceptable toxicity.
Week 1: 300 mg initial dose Week 2 through 8: 2,000 mg (once weekly) Week 12, 16, 20 and 24: 2,000 mg (every 4 weeks)
ibrutinib
ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity
Eligibility Criteria
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Inclusion Criteria
* Diagnosis of CLL or SLL that meets IWCLL 2008 criteria.
* Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment.
* Must have received at least one prior therapy for CLL/SLL.
* Considered not appropriate for treatment or retreatment with purine analog based therapy.
* Measurable nodal disease by CT.
* Patients must be able to receive outpatient treatment and laboratory monitoring at the institution that administers study drug for the entire study.
Exclusion Criteria
* No documentation of cytogenetic and/or FISH in patient records prior to first dose of study drug.
* Any history of Richter's transformation or prolymphocytic leukemia.
* Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP).
* Prior exposure to ofatumumab or to ibrutinib.
* Prior autologous transplant within 6 months prior to first dose of study drug.
* Prior allogeneic stem cell transplant within 6 months or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug.
* History of prior malignancy, with the exception of certain skin cancers and malignancies treated with curative intent and with no evidence of active disease for more than 3 years.
* Serologic status reflecting active hepatitis B or C infection.
* Unable to swallow capsules or disease significantly affecting gastrointestinal function.
* Uncontrolled active systemic fungal, bacterial, viral, or other infection.
* History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.
* Requires anticoagulation with warfarin.
18 Years
ALL
No
Sponsors
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Janssen Research & Development, LLC
INDUSTRY
Pharmacyclics LLC.
INDUSTRY
Responsible Party
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Principal Investigators
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Anita Szoke, MD
Role: STUDY_DIRECTOR
Pharmacyclics LLC.
Locations
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Site #408
La Jolla, California, United States
Site #377
Los Angeles, California, United States
Site #403
Santa Maria, California, United States
Site #038
Stanford, California, United States
Site #411
Norwalk, Connecticut, United States
Site #107
Marietta, Georgia, United States
Site # 379
Evansville, Indiana, United States
Site # 390
Boston, Massachusetts, United States
Site # 391
Boston, Massachusetts, United States
Site # 349
Boston, Massachusetts, United States
Site # 130
Detroit, Michigan, United States
Site # 406
Rochester, Minnesota, United States
Site # 059
New Brunswick, New Jersey, United States
Site # 350
New Hyde Park, New York, United States
Site # 200
New York, New York, United States
Site # 127
Rochester, New York, United States
Site # 197
Cincinnati, Ohio, United States
Site # 217
Columbus, Ohio, United States
Site # 402
Philadelphia, Pennsylvania, United States
Site # 396
Greenville, South Carolina, United States
Site # 410
Nashville, Tennessee, United States
Site # 032
Houston, Texas, United States
Site # 381
Laredo, Texas, United States
Site # 210
Charlottesville, Virginia, United States
Site # 404
Seattle, Washington, United States
Site # 500
St Leonards, New South Wales, Australia
Site # 503
Brisbane, Queensland, Australia
Site # 199
East Melbourne, Victoria, Australia
Site # 501
Fitzroy, Victoria, Australia
Site # 502
Nedlands, Western Australia, Australia
Site # 509
Graz, , Austria
Site # 508
Linz, , Austria
Site # 504
Salzburg, , Austria
Site # 505
Vienna, , Austria
Site # 506
Wein, , Austria
Site # 507
Wels, , Austria
Site # 393
Antwerp, , Belgium
Site # 519
Argenteuil, , France
Site # 511
Bobigny, , France
Site # 515
Bordeaux, , France
Site # 516
Caen, , France
Site # 513
Clermont-Ferrand, , France
Site # 510
Marseille, , France
Site # 520
Nantes, , France
Site # 518
Rennes, , France
Site # 517
Vandœuvre-lès-Nancy, , France
Site # 570
Dublin, , Ireland
Site # 528
Dublin, , Ireland
Site # 096
Galway, , Ireland
Site # 522
Milan, , Italy
Site # 523
Milan, , Italy
Site # 526
Milan, , Italy
Site # 524
Modena, , Italy
Site # 527
Padua, , Italy
Site # 529
Gdansk, , Poland
Site # 531
Lodz, , Poland
Site # 539
A Coruña, , Spain
Site # 535
Barcelona, , Spain
Site # 534
Barcelona, , Spain
Site # 533
Barcelona, , Spain
Site # 540
Madrid, , Spain
Site # 537
Madrid, , Spain
Site # 536
Madrid, , Spain
Site # 538
Pamplona, , Spain
Site # 549
Colchester, Essex, United Kingdom
Site # 543
Sutton, Surrey, United Kingdom
Site # 551
Bournemouth, , United Kingdom
Site # 553
Canterbury, , United Kingdom
Site # 546
Cardiff, , United Kingdom
Site # 554
Headington, , United Kingdom
Site # 550
Leeds, , United Kingdom
Site # 552
Liverpool, , United Kingdom
Site # 544
London, , United Kingdom
Site # 548
Nottingham, , United Kingdom
Site # 545
Southampton, , United Kingdom
Site # 541
Withington, , United Kingdom
Countries
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References
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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.
Munir T, Brown JR, O'Brien S, Barrientos JC, Barr PM, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Kipps TJ, Moreno C, Montillo M, Burger JA, Byrd JC, Hillmen P, Dai S, Szoke A, Dean JP, Woyach JA. Final analysis from RESONATE: Up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019 Dec;94(12):1353-1363. doi: 10.1002/ajh.25638. Epub 2019 Oct 13.
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.
Byrd JC, Hillmen P, O'Brien S, Barrientos JC, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Barr PM, Furman RR, Kipps TJ, Thornton P, Moreno C, Montillo M, Pagel JM, Burger JA, Woyach JA, Dai S, Vezan R, James DF, Brown JR. Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Blood. 2019 May 9;133(19):2031-2042. doi: 10.1182/blood-2018-08-870238. Epub 2019 Mar 6.
O'Brien SM, Jaglowski S, Byrd JC, Bannerji R, Blum KA, Fox CP, Furman RR, Hillmen P, Kipps TJ, Montillo M, Sharman J, Suzuki S, James DF, Chu AD, Coutre SE. Prognostic Factors for Complete Response to Ibrutinib in Patients With Chronic Lymphocytic Leukemia: A Pooled Analysis of 2 Clinical Trials. JAMA Oncol. 2018 May 1;4(5):712-716. doi: 10.1001/jamaoncol.2017.5604.
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.
Barr PM, Brown JR, Hillmen P, O'Brien S, Barrientos JC, Reddy NM, Coutre S, Mulligan SP, Jaeger U, Furman RR, Cymbalista F, Montillo M, Dearden C, Robak T, Moreno C, Pagel JM, Burger JA, Suzuki S, Sukbuntherng J, Cole G, James DF, Byrd JC. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. Blood. 2017 May 11;129(19):2612-2615. doi: 10.1182/blood-2016-12-737346. Epub 2017 Apr 3.
Maddocks KJ, Ruppert AS, Lozanski G, Heerema NA, Zhao W, Abruzzo L, Lozanski A, Davis M, Gordon A, Smith LL, Mantel R, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Awan F, Blum KA, Grever MR, Johnson AJ, Byrd JC, Woyach JA. Etiology of Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic Lymphocytic Leukemia. JAMA Oncol. 2015 Apr;1(1):80-7. doi: 10.1001/jamaoncol.2014.218.
Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17;371(3):213-23. doi: 10.1056/NEJMoa1400376. Epub 2014 May 31.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2012-000694-23
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PCYC-1112-CA
Identifier Type: -
Identifier Source: org_study_id