High Risk Chronic Lymphocytic Leukemia MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Acerta Pharma BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Men and women = 18 years of age. •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. •Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008): oMonoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing = 1 B-cell marker (CD19, CD20, or CD23) and CD5. oProlymphocytes may comprise = 55% of blood lymphocytes. o Presence of = 5 x 10^9 B lymphocytes/L (5000 µin the peripheral blood (at any point since diagnosis); this applies to CLL only. •Must have = 1 of the following high-risk prognostic factors: oPresence of 17p del by central laboratory oPresence of 11q del by central laboratory •Active disease meeting = 1 of the following IWCLL 2008 criteria for requiring treatment: Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin 50% over a 2-month period or a lymphocyte doubling time (LDT) of 1 month before Screening without evidence of infection. •Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as = 1 lymph node > 1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended. •Must have received = 1 prior therapies for CLL. •Meet the following laboratory parameters: oAbsolute neutrophil count (ANC) = 750 cells/µL (0.75 x 10^9/L) or = 500 cells/µL (0.50 x 10^9/L) in subjects with documented bone marrow involvement and independent of growth factor support 7 days before assessment. oPlatelet count = 30,000 cells/µL (30 x 10^9/L) without transfusion support 7 days bef
Exclusion criteria
Exclusion criteria: •Known central nervous system (CNS) lymphoma or leukemia. •Known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome. •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). •Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor (eg, Bruton tyrosine kinase [Btk] inhibitors or phosphoinositide-3 [PI3] kinase inhibitors or Syk inhibitors) or a BCL-2 inhibitor (eg, ABT-199). •Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug. •Corticosteroid use > 20 mg within 1 week before 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. For example, subjects 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. •Prior radio- or toxin-conjugated antibody therapy. •Prior allogeneic stem cell transplant or autologous transplant. •Major surgery within 4 weeks before first dose of study drug. •History of prior malignancy except for the following: oMalignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician oAdequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer oAdequately treated cervical carcinoma in situ without current evidence of disease •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or QTc > 480 msec at screening. •Currently active clinically significant cardiovascular disease such as uncontrolled or symptomatic 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 before first dose with study drug. •Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. •Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment. •Known history of infection with human immunodeficiency virus (HIV). •Serologic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether ACP-196 is non-inferior to ibrutinib with respect to progression-free survival (PFS) based on independent review committee (IRC) assessment in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) with high-risk prognostic markers.; Secondary Objective: To evaluate the benefit:risk of ACP-196 versus ibrutinib in terms of: •Grade = 3 infections •Richter’s transformation •Atrial fibrillation •Overall survival (OS) Safety Objectives: •Safety and tolerability including adverse events (AEs) of interest and laboratory assessments Exploratory Objectives: •IRC-assessed overall response rate (ORR) per IWCLL 2008 criteria •Investigator-assessed PFS and ORR per IWCLL 2008 criteria •Improvement and/or resolution of disease-related symptoms •Improvement in incidence of diarrhea, major bleeding events, lymphocytosis, and second primary malignancy •Patient-reported outcome (PRO) by various scales •Medical resource utilization (MRU) •Pharmacokinetic (PK) characteristics of ACP-196 in subjects with CLL to determine which, if any, covariates (eg, age, sex, body size, race) influence exposure to ACP-196 •Potential predictive biomarkers and mechanisms of resistance for the disease ;Primary end point(s): To assess whether ACP-196 is non-inferior to ibrutinib with respect to progression-free survival (PFS) based on independent review committee (IRC) assessment in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL) with high-risk prognostic markers. ;Timepoint(s) of evaluation of this end point: 48 months - estimated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare between ACP-196 and ibrutinib in terms of: •Incidence of Grade = 3 infections •Incidence of Richter’s transformation •Incidence of atrial fibrillation •OS ;Timepoint(s) of evaluation of this end point: estimated 48 months | — |
Countries
Australia, Belgium, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactKellie Macleod
PPD
Outcome results
None listed