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Relapsed or Refractory Chronic Lymphocytic LeukemiaPhase 3RESONATE™NCT01578707

A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

A Phase 3 study testing ofatumumab and ibrutinib in people with Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Pharmacyclics LLC. at 76 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ofatumumab and ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
391 participants
Where
76 sitesin 10 countries
Study dates
Jun 2012to 25 Oct 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

76 sites in 10 countries.

76 sites in 10 countries

United States25 sites

  • Site # 390

    Boston, Massachusetts, 02114

  • Site # 391

    Boston, Massachusetts, 02115

  • Site # 349

    Boston, Massachusetts, 02215

  • Site # 210

    Charlottesville, Virginia, 22908

  • Site # 197

    Cincinnati, Ohio, 45291

  • Site # 217

    Columbus, Ohio, 43210

  • Site # 130

    Detroit, Michigan, 48201

  • Site # 379

    Evansville, Indiana, 47713

  • Site # 396

    Greenville, South Carolina, 29601

  • Site # 032

    Houston, Texas, 77030

  • Site #408

    La Jolla, California, 92093-0698

  • Site # 381

    Laredo, Texas, 78041

  • Site #377

    Los Angeles, California, 90095

  • Site #107

    Marietta, Georgia, 30060

  • Site # 410

    Nashville, Tennessee, 37232-5505

  • Site # 059

    New Brunswick, New Jersey, 08903

  • Site # 350

    New Hyde Park, New York, 11042

  • Site # 200

    New York, New York, 10065

  • Site #411

    Norwalk, Connecticut, 06856

  • Site # 402

    Philadelphia, Pennsylvania, 19104

  • Site # 406

    Rochester, Minnesota, 55901

  • Site # 127

    Rochester, New York, 14642-0001

  • Site #403

    Santa Maria, California, 93454

  • Site # 404

    Seattle, Washington, 98109

  • Site #038

    Stanford, California, 94035

Other trials in United States

United Kingdom12 sites

  • Site # 551

    Bournemouth, BH7 7DW

  • Site # 553

    Canterbury, CT1 3NG

  • Site # 546

    Cardiff, CF14 4XW

  • Site # 549

    Colchester, Essex, CO4 5JL

  • Site # 554

    Headington, OX3 7LJ

  • Site # 550

    Leeds, LS9 7TF

  • Site # 552

    Liverpool, L7 8XP

  • Site # 544

    London, SE5 9RS

  • Site # 548

    Nottingham, NG5 1PB

  • Site # 545

    Southampton, SO16 6YD

  • Site # 543

    Sutton, Surrey, SM2 5PT

  • Site # 541

    Withington, M20 4BX

Other trials in United Kingdom

France9 sites

  • Site # 519

    Argenteuil, 95107

  • Site # 511

    Bobigny, 93009

  • Site # 515

    Bordeaux, 33076

  • Site # 516

    Caen, 14033

  • Site # 513

    Clermont-Ferrand, 63100

  • Site # 510

    Marseille, 13273

  • Site # 520

    Nantes, 44000

  • Site # 518

    Rennes, 35033

  • Site # 517

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Spain8 sites

  • Site # 539

    A Coruña, 15006A

  • Site # 535

    Barcelona, 08025

  • Site # 534

    Barcelona, 08035

  • Site # 533

    Barcelona, 08036

  • Site # 540

    Madrid, 28033

  • Site # 537

    Madrid, 28050

  • Site # 536

    Madrid, 28222

  • Site # 538

    Pamplona, 31008

Other trials in Spain

Austria6 sites

  • Site # 509

    Graz, 8036

  • Site # 508

    Linz, 4010

  • Site # 504

    Salzburg, 5020

  • Site # 505

    Vienna, A-1090

  • Site # 506

    Wein, 1160

  • Site # 507

    Wels, A-4600

Other trials in Austria

Australia5 sites

  • Site # 503

    Brisbane, Queensland, 4102

  • Site # 199

    East Melbourne, Victoria, 3002

  • Site # 501

    Fitzroy, Victoria, 3109

  • Site # 502

    Nedlands, Western Australia, 6009

  • Site # 500

    St Leonards, New South Wales, 2065

Other trials in Australia

Italy5 sites

  • Site # 522

    Milan, 20089

  • Site # 523

    Milan, 20132

  • Site # 526

    Milan, 20162

  • Site # 524

    Modena, 41124

  • Site # 527

    Padova, 35128

Other trials in Italy

Ireland3 sites

  • Site # 570

    Dublin, 8

  • Site # 528

    Dublin, 9

  • Site # 096

    Galway

Other trials in Ireland

Poland2 sites

  • Site # 529

    Gdansk, 80-952

  • Site # 531

    Lodz, 93-510

Other trials in Poland

Belgium1 site

  • Site # 393

    Antwerp, 2060

Other trials in Belgium

About this study

Official title: 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

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)

Read the 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.

Being tested
ofatumumab, ibrutinib
Keywords
Chronic, SLL, CLL, Ofatumumab, ibrutinib, RESONATE, Phase III, Leukemia, Lymphoma
Medical subject headings
Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell, Bronchiolitis Obliterans Syndrome, Leukemia, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ofatumumabDrug

    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)

  • ibrutinibDrug

    ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

Study groups in NCT01578707
Study groupRoleWhat they receive
Ofatumumab (Arm A)Active comparatorAn anti-CD20 monoclonal antibody
Receives: Drug: ofatumumab
ibrutinib (Arm B)ExperimentalA Bruton Tyrosine Kinase Inhibitor
Receives: Drug: ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013

    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.

    Measured: Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled.

Secondary outcomes (3)

  1. Overall Response Rate (ORR) by Independent Review Committee (IRC)

    Overall Response Rate per the IWCLL 2008 criteria as assessed by IRC, limited to the time of primary analysis 06 November 2013

    Measured: About 18 months after the first subject was enrolled

  2. OS (Overall Survival)

    OS analysis was conducted at the time of study closure, with no adjustment for crossover from the ofatumumab arm to the ibrutinib arm

    Measured: OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up

  3. Rate of Sustained Hemoglobin and Platelet Improvement

    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.

    Measured: From study initiation to study closure, including up to 6 years of study follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionNov 2013
  4. Study completion25 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
391 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01578707
Sponsor's protocol ID
PCYC-1112-CA
Other IDs
2012-000694-23
Acronym
RESONATE™
Status last verified
Dec 2019
First submitted
11 Apr 2012
Last updated
18 Dec 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 40266025

  • 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.

    PubMed 31512258

  • 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.

    PubMed 31196847

  • 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.

    PubMed 30842083

  • 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.

    PubMed 29470582

  • 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.

    PubMed 28751558

  • 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.

    PubMed 28373262

  • 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.

    PubMed 26182309

  • 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.

    PubMed 24881631

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ofatumumab and ibrutinib in people with Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Pharmacyclics LLC. at 76 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, United Kingdom, France, Spain, Austria and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01578707, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2019.

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