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
  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 will be conducted after observing approximately 117 PFS events ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 391
Study Start Date: June 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2015 (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 who experience disease progression (PD) may be considered to receive next subsequent therapy with ibrutinib.

  Eligibility

Ages Eligible for Study:   18 Years and older
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

Locations
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Pharmacyclics
Janssen Research & Development, LLC
Investigators
Study Director: Danelle James, MD Pharmacyclics
  More Information

No publications provided by Pharmacyclics

Additional 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
Last Updated: March 7, 2014
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: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
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:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 30, 2014