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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: March 7, 2014
Last verified: March 2014

April 11, 2012
March 7, 2014
June 2012
July 2015   (final data collection date for primary outcome measure)
PFS (Progression Free Survival) [ Time Frame: Analysis will be conducted after observing approximately 117 PFS events ] [ Designated as safety issue: No ]
PFS (Progression Free Survival) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01578707 on ClinicalTrials.gov Archive Site
  • OS (Overall Survival) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Hematological Improvements [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Improvement of disease-related symptoms (fatigue, night sweats, and splenomegaly). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • ORR (Overall Response Rate) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • OS (Overall Survival) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Hematological Improvements [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Investigator-assessed PFS [ Time Frame: Time from randomization until disease progression ] [ Designated as safety issue: No ]
  • Investigator-assessed ORR [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Improvement of disease-related symptoms (fatigue, night sweats, and splenomegaly). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Phase 3 Study of Ibrutinib (PCI-32765) Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
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)

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 who experience disease progression (PD) may be considered to receive next subsequent therapy with ibrutinib.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Relapsed or Refractory Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • 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)

  • Drug: ibrutinib
    ibrutinib 420 mg (3 x 140-mg capsules) will be administered orally once daily until disease progression or unacceptable toxicity
  • Active Comparator: Ofatumumab (Arm A)
    An anti-CD20 monoclonal antibody
    Intervention: Drug: ofatumumab
  • Experimental: ibrutinib (Arm B)
    A Bruton Tyrosine Kinase Inhibitor
    Intervention: Drug: ibrutinib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
391
December 2015
July 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01578707
PCYC-1112-CA, 2012-000694-23
Yes
Pharmacyclics
Pharmacyclics
Janssen Research & Development, LLC
Study Director: Danelle James, MD Pharmacyclics
Pharmacyclics
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP