Untreated Chronic Lymphocytic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Calquence 100mg Capsules
Product Name: acalabrutinib
Product Code: ACP-196
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Acalabrutinib
CAS Number: 1420477-60-6
Current Sponsor co
Sponsors
Acerta Pharma BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Men and women = 65 years of age, or > 18 and 50% over a 2-month period or a lymphocyte doubling time (LDT) of 1 month before Screening without evidence of infection. • Meet the following laboratory parameters: o Absolute neutrophil count = 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. o Platelet count = 50,000 cells/µL (50 x 10^9/L), or = 30,000 cells/µL (30 x 10^9/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded. o Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3.0 x upper limit of normal (ULN). o Total bilirubin = 1.5 x ULN. o Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) = 30 mL/min. • Able to receive all outpatient treatment, all laboratory monitoring, and all radiologic evaluations. • Women who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib or 18 months after the last dose
Exclusion criteria
Exclusion criteria: • Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed). • Known central nervous system (CNS) lymphoma or leukemia. • Known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome. • Missing or incomplete documentation of FISH results reflecting the presence or absence of 17p del and the percentage of cells with the deletion in subject records before randomization. • 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). • 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 (WBC) lowering are excluded. • Major surgery within 4 weeks before first dose of study drug. • History of prior malignancy except for the following: o Malignancy 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. o Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer. o Adequately 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. • Unable to swallow capsules or tablets 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). • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. • Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before randomization. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded. • History of stroke or intracranial hemorrhage within 6 months before randomization. • History of a bleeding diathesis (eg, hemophilia, von Willebrand disease). • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug. • Requires treatment wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B), based on IRC assessment of PFS per IWCLL 2008 criteria, in subjects with previously untreated CLL.;Secondary Objective: - To evaluate the efficacy of Arm A versus acalabrutinib monotherapy (Arm C) based on IRC assessment of PFS per IWCLL 2008 criteria. - To compare Arm A versus Arm B and Arm A versus Arm C in terms of: • IRC-assessed objective response rate (ORR) per IWCLL 2008 criteria. • Time to next treatment (TTNT) (defined as the time from randomization to institution of non-protocol specified treatment for CLL). • Overall survival (OS).;Primary end point(s): The primary endpoint of the study is PFS as assessed by IRC review per IWCLL 2008 criteria. The primary analysis is a comparison of PFS between Arm A and Arm B.;Timepoint(s) of evaluation of this end point: TBC | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: The first secondary endpoint is a comparison of IRC-assessed PFS between Arm A and Arm C. Other secondary endpoints are as follows and compare Arm A versus Arm B and Arm A versus Arm C in terms of: • ORR defined as complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), or partial remission (PR) (per IWCLL 2008 criteria). • TTNT (defined as the time from randomization to institution of non-protocol specified treatment for CLL). • OS. Safety: • Frequency, severity, and relatedness of adverse events. • Frequency of adverse events requiring discontinuation of study drug or dose reductions. • Change in laboratory assessments.;Timepoint(s) of evaluation of this end point: TBC | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, Colombia, France, Germany, Hungary, Israel, Italy, Lithuania, New Zealand, Poland, Spain, Sweden, United Kingdom, United States
Outcome results
None listed