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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01578707
Recruitment Status : Completed
First Posted : April 17, 2012
Results First Posted : October 12, 2015
Last Update Posted : December 18, 2019
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Description
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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)

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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 391 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : June 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : October 25, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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. ]
    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 :
  1. Overall Response Rate (ORR) by Independent Review Committee (IRC) [ Time Frame: 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

  2. OS (Overall Survival) [ Time Frame: 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

  3. Rate of Sustained Hemoglobin and Platelet Improvement [ Time Frame: 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.


Other Outcome Measures:
  1. 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 ]
    Long-Term Progression Free Survival as assessed by the investigator with up to 6 years of study follow-up

  2. Overall Response Rate (ORR) by Investigator [ Time Frame: From study initiation to study closure, including up to 6 years of study follow-up ]
    Overall response per the IWCLL 2008 criteria as assessed by Investigator with up to 6 years of study follow-up


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01578707


Locations
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Sponsors and Collaborators
Pharmacyclics LLC.
Janssen Research & Development, LLC
Investigators
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Study Director: Anita Szoke, MD Pharmacyclics LLC.
  Study Documents (Full-Text)

Documents provided by Pharmacyclics LLC.:
Study Protocol  [PDF] September 28, 2016
Statistical Analysis Plan  [PDF] April 25, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01578707    
Other Study ID Numbers: PCYC-1112-CA
2012-000694-23 ( EudraCT Number )
First Posted: April 17, 2012    Key Record Dates
Results First Posted: October 12, 2015
Last Update Posted: December 18, 2019
Last Verified: December 2019
Keywords provided by Pharmacyclics LLC.:
Chronic
SLL
CLL
Ofatumumab
ibrutinib
 RESONATE
Phase III
Leukemia
Lymphoma
Additional relevant MeSH terms:
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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
Chronic Disease
Disease Attributes
Pathologic Processes
Ofatumumab
Antineoplastic Agents