TriangleNCT01578707 · CITED IN SOURCE DOCUMENTS
A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2019-12-18
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)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013
Overall Response Rate (ORR) by Independent Review Committee (IRC)
OS (Overall Survival)
Rate of Sustained Hemoglobin and Platelet Improvement
Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up
Overall Response Rate (ORR) by Investigator
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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. Exclusion Criteria: * 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- An anti-CD20 monoclonal antibody
- intervention Names
- Drug: ofatumumab
- label
- Ofatumumab (Arm A)
- type
- ACTIVE_COMPARATOR
- description
- A Bruton Tyrosine Kinase Inhibitor
- intervention Names
- Drug: ibrutinib
- label
- ibrutinib (Arm B)
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Ofatumumab (Arm A)
- description
- 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)
- name
- ofatumumab
- type
- DRUG
- arm Group Labels
- ibrutinib (Arm B)
- description
- ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity
- name
- ibrutinib
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 391
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up
- measure
- Progression Free Survival (PFS) by Investigator With up to 6 Years of Study Follow-up
- time Frame
- From study initiation to study closure, including up to 6 years of study follow-up
- description
- Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up
- measure
- Overall Response Rate (ORR) by Investigator
- time Frame
- From study initiation to study closure, including up to 6 years of study follow-up
- primary Outcomes
- description
- 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.
- measure
- PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013
- time Frame
- Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.
- secondary Outcomes
- description
- Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013
- measure
- Overall Response Rate (ORR) by Independent Review Committee (IRC)
- time Frame
- About 18 months after the first subject was enrolled
- description
- OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm
- measure
- OS (Overall Survival)
- time Frame
- OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up
- description
- 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.
- measure
- Rate of Sustained Hemoglobin and Platelet Improvement
- time Frame
- From study initiation to study closure, including up to 6 years of study follow-up
Full study description
- 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.
Source references
- references
- citation
- 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.
- pmid
- 40266025
- type
- DERIVED
- citation
- 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.
- pmid
- 31512258
- type
- DERIVED
- citation
- 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
- type
- DERIVED
- citation
- 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.
- pmid
- 30842083
- type
- DERIVED
- citation
- 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.
- pmid
- 29470582
- type
- DERIVED
- citation
- 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.
- pmid
- 28751558
- type
- DERIVED
- citation
- 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.
- pmid
- 28373262
- type
- DERIVED
- citation
- 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.
- pmid
- 26182309
- type
- DERIVED
- citation
- 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.
- pmid
- 24881631
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-ac4e3c50fb9d9c2b5207
- requested nct id
- NCT01578707
- primary nct id
- NCT01578707
- source kind
- fda_spl_label
- source record id
- 43280dcb-52ae-40e4-bd52-723f71f74ab7
- source file sha256
- d918de6bede8f776ad4fea2bc639292f8454d9733fbbdfdd7fd4414b6200e571
- payload sha256
- f5f12fd95f1314d0de79366f7696f8ab5ff14fc636646f5c82452d6f283c8a6b
- payload
- application numbers
- NDA217003
- NDA210563
- NDA205552
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-ac4e3c50fb9d9c2b5207
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT01578707
- occurrences
- context exact
- 24.2+ months. The median DOR was not reached. RESONATE The RESONATE study, a randomized, multicenter, open-label, phase 3 study of IMBRUVICA versus ofatumumab (NCT01578707), was conducted in patients with previously treated CLL or SLL. Patients (n=391) were randomized 1:1 to receive either IMBRUVICA 420 mg daily until disease pro
- end
- 1973
- exact text
- NCT01578707
- start
- 1962
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00200.json
- source file sha256
- d918de6bede8f776ad4fea2bc639292f8454d9733fbbdfdd7fd4414b6200e571
- source json pointer
- /results/56/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 43280dcb-52ae-40e4-bd52-723f71f74ab7
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 2a0a06d7967191ffa726d265162eddf5957b21c7bd85d46aa24c2ce31199d5c0
- spl effective time
- 20251021
- spl set id
- 0dfd0279-ff17-4ea9-89be-9803c71bab44
Preserved source evidence · Not medical advice