A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
- Conditions
- Relapsed or Refractory Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT01578707
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
The purpose of the study is to evaluate whether treatment with ibrutinib as a monotherapy results in a clinically significant improvement in progression free survival (PFS) as compared to treatment with ofatumumab in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
- Detailed Description
Study PCYC-1112-CA is a randomized, multicenter, open-label, phase 3 study of the Bruton's Tyrosine Kinase (BTK) inhibitor Ibrutinib (PCI-32765) versus Ofatumumab in patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Patients randomized to the ofatumumab arm may be considered to receive next subsequent therapy with ibrutinib.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 391
- ECOG performance status of 0-1.
- 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.
- Known CNS lymphoma or leukemia.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ofatumumab (Arm A) ofatumumab An anti-CD20 monoclonal antibody ibrutinib (Arm B) ibrutinib A Bruton Tyrosine Kinase Inhibitor
- Primary Outcome Measures
Name Time Method PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013 Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled. The primary objective of this study was to evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) according to 2008 IWCLL guidelines.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) by Independent Review Committee (IRC) About 18 months after the first subject was enrolled Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013
OS (Overall Survival) OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm
Rate of Sustained Hemoglobin and Platelet Improvement From study initiation to study closure, including up to 6 years of study follow-up Proportion of subjects with hemoglobin (HgB) increase \>=20 g/L and platelet (PLT) increase \>=50% over baseline continuously for \>=56 days without blood transfusions or growth factors.
Trial Locations
- Locations (76)
Site # 059
🇺🇸New Brunswick, New Jersey, United States
Site # 501
🇦🇺Fitzroy, Victoria, Australia
Site #408
🇺🇸La Jolla, California, United States
Site # 509
🇦🇹Graz, Austria
Site #411
🇺🇸Norwalk, Connecticut, United States
Site # 515
🇫🇷Bordeaux, France
Site # 510
🇫🇷Marseille, France
Site #107
🇺🇸Marietta, Georgia, United States
Site # 540
🇪🇸Madrid, Spain
Site # 531
🇵🇱Lodz, Poland
Site # 504
🇦🇹Salzburg, Austria
Site # 507
🇦🇹Wels, Austria
Site # 506
🇦🇹Wein, Austria
Site # 552
🇬🇧Liverpool, United Kingdom
Site # 127
🇺🇸Rochester, New York, United States
Site #377
🇺🇸Los Angeles, California, United States
Site #038
🇺🇸Stanford, California, United States
Site #403
🇺🇸Santa Maria, California, 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 # 350
🇺🇸New Hyde Park, New York, United States
Site # 200
🇺🇸New York, New York, United States
Site # 197
🇺🇸Cincinnati, Ohio, United States
Site # 217
🇺🇸Columbus, Ohio, United States
Site # 402
🇺🇸Philadelphia, Pennsylvania, United States
Site # 410
🇺🇸Nashville, Tennessee, United States
Site # 032
🇺🇸Houston, Texas, United States
Site # 396
🇺🇸Greenville, South Carolina, United States
Site # 381
🇺🇸Laredo, Texas, United States
Site # 210
🇺🇸Charlottesville, Virginia, United States
Site # 500
🇦🇺St. Leonards, New South Wales, Australia
Site # 404
🇺🇸Seattle, Washington, United States
Site # 503
🇦🇺Brisbane, Queensland, Australia
Site # 502
🇦🇺Nedlands, Western Australia, Australia
Site # 199
🇦🇺East Melbourne, Victoria, Australia
Site # 393
🇧🇪Antwerpen, Belgium
Site # 505
🇦🇹Vienna, Austria
Site # 508
🇦🇹Linz, Austria
Site # 519
🇫🇷Argenteuil, France
Site # 511
🇫🇷Bobigny, France
Site # 513
🇫🇷Clermont Ferrand, France
Site # 516
🇫🇷Caen, France
Site # 096
🇮🇪Galway, Ireland
Site # 570
🇮🇪Dublin, Ireland
Site # 520
🇫🇷Nantes, France
Site # 528
🇮🇪Dublin, Ireland
Site # 517
🇫🇷Vandœuvre-lès-Nancy, France
Site # 518
🇫🇷Rennes, France
Site # 522
🇮🇹Milano, Italy
Site # 523
🇮🇹Milano, Italy
Site # 526
🇮🇹Milano, Italy
Site # 524
🇮🇹Modena, Italy
Site # 529
🇵🇱Gdansk, Poland
Site # 527
🇮🇹Padova, Italy
Site # 535
🇪🇸Barcelona, Spain
Site # 539
🇪🇸Coruna, Spain
Site # 534
🇪🇸Barcelona, Spain
Site # 533
🇪🇸Barcelona, Spain
Site # 537
🇪🇸Madrid, Spain
Site # 538
🇪🇸Pamplona, Spain
Site # 536
🇪🇸Madrid, Spain
Site # 549
🇬🇧Colchester, Essex, United Kingdom
Site # 543
🇬🇧Sutton, Surrey, United Kingdom
Site # 553
🇬🇧Canterbury, United Kingdom
Site # 551
🇬🇧Bournemouth, United Kingdom
Site # 546
🇬🇧Cardiff, United Kingdom
Site # 554
🇬🇧Headington, United Kingdom
Site # 550
🇬🇧Leeds, United Kingdom
Site # 548
🇬🇧Nottingham, United Kingdom
Site # 544
🇬🇧London, United Kingdom
Site # 545
🇬🇧Southampton, United Kingdom
Site # 541
🇬🇧Withington, United Kingdom