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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01578707
First received: April 11, 2012
Last updated: September 11, 2015
Last verified: September 2015
  Purpose
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)

Condition Intervention Phase
Relapsed or Refractory Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: ofatumumab
Drug: ibrutinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • PFS (Progression Free Survival) [ Time Frame: Analysis was conducted after observing approximately 117 PFS events, which occurred about 18 months after the first subject was enrolled. ] [ Designated as safety issue: No ]

    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).

    Progressive disease according to 2008 IWCLL guidelines was defined as:

    • Group A

      • Lymphadenopathy, increase ≥50%
      • Hepatomegaly, increase ≥50%
      • Splenomegaly, increase ≥50%
      • Blood lymphocytes, increase ≥ 50% over baseline
    • Group B

      • Platelets counts, decrease of ≥ 50% from baseline secondary to CLL
      • Hemoglobin, decrease of > 2 g/dL from baseline secondary to CLL


Secondary Outcome Measures:
  • OS (Overall Survival) [ Time Frame: OS analysis was conducted at the time of the interim PFS analysis, which was about 18 months after the first subject was enrolled. ] [ Designated as safety issue: No ]
  • Hematological Improvements [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 391
Study Start Date: June 2012
Estimated Study Completion Date: December 2017
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ofatumumab (Arm A)
An anti-CD20 monoclonal antibody
Drug: 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)

Experimental: ibrutinib (Arm B)
A Bruton Tyrosine Kinase Inhibitor
Drug: ibrutinib
ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01578707

  Hide Study Locations
Locations
United States, California
Site #408
La Jolla, California, United States, 92093-0698
Site #377
Los Angeles, California, United States, 90095
Site #403
Santa Maria, California, United States, 93454
Site #038
Stanford, California, United States, 94035
United States, Connecticut
Site #411
Norwalk, Connecticut, United States, 06856
United States, Georgia
Site #107
Marietta, Georgia, United States, 30060
United States, Indiana
Site # 379
Evansville, Indiana, United States, 47713
United States, Massachusetts
Site # 390
Boston, Massachusetts, United States, 02114
Site # 391
Boston, Massachusetts, United States, 02115
Site # 349
Boston, Massachusetts, United States, 02215
United States, Michigan
Site # 130
Detroit, Michigan, United States, 48201
United States, Minnesota
Site # 406
Rochester, Minnesota, United States, 55901
United States, New Jersey
Site # 059
New Brunswick, New Jersey, United States, 08903
United States, New York
Site # 350
New Hyde Park, New York, United States, 11042
Site # 200
New York, New York, United States, 10065
Site # 127
Rochester, New York, United States, 14642-0001
United States, Ohio
Site # 197
Cincinnati, Ohio, United States, 45291
Site # 217
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Site # 402
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Site # 396
Greenville, South Carolina, United States, 29601
United States, Tennessee
Site # 410
Nashville, Tennessee, United States, 37232-5505
United States, Texas
Site # 032
Houston, Texas, United States, 77030
Site # 381
Laredo, Texas, United States, 78041
United States, Virginia
Site # 210
Charlottesville, Virginia, United States, 22908
United States, Washington
Site # 404
Seattle, Washington, United States, 98109
Australia, New South Wales
Site # 500
St. Leonards, New South Wales, Australia, 2065
Australia, Queensland
Site # 503
Brisbane, Queensland, Australia, 4102
Australia, Victoria
Site # 501
Fitzroy, Victoria, Australia, 3109
Australia, Western Australia
Site # 502
Nedlands, Western Australia, Australia, 6009
Australia
Site # 199
Victoria, Australia, 3002
Austria
Site # 509
Graz, Austria, 8036
Site # 508
Linz, Austria, 4010
Site # 504
Salzburg, Austria, 5020
Site # 505
Vienna, Austria, A-1090
Site # 506
Wein, Austria, 1160
Site # 507
Wels, Austria, A-4600
Belgium
Site # 393
Antwerpen, Belgium, 2060
France
Site # 519
Argenteuil, France, 95107
Site # 511
Bobigny, France, 93009
Site # 515
Bordeaux, France, 33076
Site # 516
Caen, France, 14033
Site # 513
Clermont Ferrand, France, 63100
Site # 510
Marseille, France, 13273
Site # 520
Nantes, France, 44000
Site # 518
Rennes, France, 35033
Site # 517
Vandoeuvre, France, 54511
Ireland
Site # 570
Dublin, Ireland, 8
Site # 528
Dublin, Ireland, 9
Site # 096
Galway, Ireland
Italy
Site # 522
Milano, Italy, 20089
Site # 523
Milano, Italy, 20132
Site # 526
Milano, Italy, 20162
Site # 524
Modena, Italy, 41124
Site # 527
Padova, Italy, 35128
Poland
Site # 529
Gdansk, Poland, 80-952
Site # 531
Lodz, Poland, 93-510
Spain
Site # 533
Barcelona, Spain, 08036
Site # 535
Barcelona, Spain, 08025
Site # 534
Barcelona, Spain, 08035
Site # 539
Coruna, Spain, 15006A
Site # 540
Madrid, Spain, 28033
Site # 537
Madrid, Spain, 28050
Site # 536
Madrid, Spain, 28222
Site # 538
Pamplona, Spain, 31008
United Kingdom
Site # 549
Colchester, Essex, United Kingdom, CO4 5JL
Site # 551
Bournemouth, United Kingdom, BH7 7DW
Site # 553
Canterbury, United Kingdom, CT1 3NG
Site # 546
Cardiff, United Kingdom, CF14 4XW
Site # 554
Headington, United Kingdom, OX3 7LJ
Site # 550
Leeds, United Kingdom, LS9 7TF
Site # 552
Liverpool, United Kingdom, L7 8XP
Site # 544
London, United Kingdom, SE5 9RS
Site # 548
Nottingham, United Kingdom, NG5 1PB
Site # 545
Southampton, United Kingdom, SO16 6YD
Site # 543
Surrey, United Kingdom, SM2 5PT
Site # 541
Withington, United Kingdom, M20 4BX
Sponsors and Collaborators
Pharmacyclics
Janssen Research & Development, LLC
Investigators
Study Director: George Cole, MD Pharmacyclics
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01578707     History of Changes
Other Study ID Numbers: PCYC-1112-CA  2012-000694-23 
Study First Received: April 11, 2012
Results First Received: June 23, 2015
Last Updated: September 11, 2015
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
France: ANSM, National Safety Agency for Medicinal Product and Health Services
Ireland: Health Products Regulatory Authority
Italy: The Italian Medicines Agency
Poland: The Central Register of Clinical Trials
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Pharmacyclics:
Chronic
SLL
CLL
Ofatumumab
ibrutinib
RESONATE
Phase III
Leukemia
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2016