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
Overview
- Phase
- Phase 3
- Intervention
- ibrutinib
- Conditions
- Relapsed or Refractory Chronic Lymphocytic Leukemia
- Sponsor
- Pharmacyclics LLC.
- Enrollment
- 391
- Locations
- 76
- Primary Endpoint
- PFS (Progression Free Survival) by Independent Review Committee (IRC), Limited to the Time of Primary Analysis 06 November 2013
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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)
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •ECOG performance status of 0-
- •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.
Arms & Interventions
ibrutinib (Arm B)
A Bruton Tyrosine Kinase Inhibitor
Intervention: ibrutinib
Ofatumumab (Arm A)
An anti-CD20 monoclonal antibody
Intervention: ofatumumab
Outcomes
Primary Outcomes
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 Outcomes
- Overall Response Rate (ORR) by Independent Review Committee (IRC)(About 18 months after the first subject was enrolled)
- OS (Overall Survival)(OS analysis was conducted at the time of study closure, including up to 6 years of study follow-up)
- Rate of Sustained Hemoglobin and Platelet Improvement(From study initiation to study closure, including up to 6 years of study follow-up)