relapsed or refractory CLL/SLL MedDRA version: 19.0 Level: LLT Classification code 10060671 Term: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma refractory System Organ Class: 100000004864
Conditions
Sponsors
Pharmacyclics LLC an Abbvie Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: • Eastern Cooperative Oncology Group (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. • Must not be appropriate for treatment or retreatment with purine analog based therapy. • Measurable nodal disease by CT. • Must have the following laboratory parameters met for inclusion: - Absolute neutrophil count (ANC) = 750 cells/µL (0.75 x 109/L), independent of growth factor support. - Platelet count = 30,000 cells/µL (30 x 109/L) without transfusion support. - Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) =65 years) yes F.1.3.1 Number of subjects for this age range 280
Exclusion criteria
Exclusion criteria: Patients will be ineligible for this study if they meet any of the following criteria: 1. Known central nervous system (CNS) lymphoma or leukemia 2. Known prolymphocytic leukemia or history of or currently suspected Richter’s transformation 3. Missing or incomplete documentation of cytogenetic and/or FISH results reflecting the presence or absence of 17p del and the percentage of cells with the deletion in patient records prior to randomization 4. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (>20 mg daily of prednisone daily or equivalent). 5. Prior exposure to ofatumumab or to ibrutinib (PCI-32765) or randomization into an ibrutinib study 6. Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug 7. Corticosteroid use > 20 mg within 1 week prior to first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Patients requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded 8. Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug 9. Prior autologous transplant within 6 months prior to first dose of study drug 10. Prior allogeneic stem cell transplant within 6 months prior to randomization or with any evidence of active graft versus host disease or requirement for immunosuppressants within 28 days prior to first dose of study drug. 11. Major surgery within 4 weeks prior to first dose of study drug 12. History of prior malignancy, with the exception of the following: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician b) Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer c) Adequately treated cervical carcinoma in situ without current evidence of disease 13. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months prior to first dose with study drug 14. Unable to swallow capsules or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine 15. Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ibrutinib compared to ofatumumab based on independent review committee (IRC) assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia Criteria (IWCLL, Hallek 2008) with incorporation of the clarification for treatment related lymphocytosis (Hallek 2012) (hereafter referred to as IWCLL 2008 criteria) in patients with relapsed or refractory CLL/SLL.; Secondary Objective: Efficacy • To evaluate overall survial (OS) • To evaluate IRC-assessed overall response rate (ORR) per IWCLL 2008 criteria • To evaluate patient-reported outcome (PRO) by FACiT-Fatigue • To evaluate hematological improvement Safety • To evaluate the safety and tolerability of ibrutinib compared to of Ofatumumab ; Primary end point(s): The primary endpoint of the study is PFS, as assessed by IRC review per IWCLL 2008 criteria. ; Timepoint(s) of evaluation of this end point: Depends on PFS events as the primary endpoint of this study is PFS, as assessed by IRC review per IWCLL 2008 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare between the two treatment groups in terms of: • OS • Overall response rate (ORR) is defined as the proportion of patients who achieve compelte response (CR), complete response with Incomplete bone marrow recovery (CRi), nodular partial response (nPR), or parital response (PR) per IWCLL 2008 criteria over the course of the study as evaluated by an IRC • Patient reported outcome (PRO) as measured by FACiT-Fatigue. • The efficacy measure for the FACiT-Fatigue will be the change in scores from baseline to each assessment. • Hematological improvement in the subset of patients with cytopenia(s) at baseline assessed by time to improvement and percentage of patients with improvement. Safety • To compare the safety and tolerability between the two treatment groups ;Timepoint(s) of evaluation of this end point: Depends on PFS events as the primary endpoint of this study is PFS, as assessed by IRC review per IWCLL 2008 criteria. | — |
Countries
Australia, Austria, Belgium, France, Ireland, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactJill Herendeen
Pharmacyclics LLC an Abbvie Company
Outcome results
None listed