Relapsed or Refractory Chronic Lymphocytic Leukemia MedDRA version: 20.1 Level: LLT Classification code 10008978 Term: Chronic lymphocytic leukemia refractory System Organ Class: 100000004864
Conditions
Sponsors
Acerta Pharma BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women = 18 years of age. 2. ECOG performance status of 0 to 2. 3. Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008): a. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing = 1 B-cell marker (CD19, CD20, or CD23) and CD5. b. Prolymphocytes may comprise = 55% of blood lymphocytes. c. Presence of = 5 x 109 B lymphocytes/L (5000 µL) in the peripheral blood (at any point since initial diagnosis). 4.Must have documented CD20-positive CLL. 5.Active disease meeting = 1 of the following IWCLL 2008 criteria for requiring treatment: a. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin 50% over a 2-month period or a LDT of 1 month before screening without evidence of infection. 6. Meet the following laboratory parameters: a. Absolute neutrophil count (ANC) = 750 cells/µL (0.75 x 109/L), or = 500 cells/µL (0.50 x 109/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment. b. Platelet count = 50,000 cells/µL (50 x 109/L), or = 30,000 cells/µL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded. If an Investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be = 75,000 cells/µL (75 x 109/L). c. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.0 x upper limit of normal (ULN). d. Total bilirubin = 1.5 x ULN. e. Estimated creatinine clearance of = 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female]. 7.Must have received = 1 prior systemic therapies for CLL. Note: Single-agent steroids or localized radiation are not considered a prior line of therapy. If a single- agent anti-CD20 antibody was previously administered, subjects must have received = 2 doses. 8.Able to receive all outpatient treatment, all laboratory monitoring, and all radio
Exclusion criteria
Exclusion criteria: 1.Known CNS lymphoma or leukemia. 2.Known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome. 3.Uncontrolled AIHA or 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 or equivalent). 4.Prior exposure to a BCL-2 inhibitor (eg, ABT-199) or a BCR inhibitor (eg, Btk inhibitors or PI3K inhibitors). 5.Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug. 6.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. 7.Prior radio- or toxin-conjugated antibody therapy. 8.Prior allogeneic stem cell transplant or prior autologous transplant within 6 months of first dose of study drug(s) or presence of graft-vs-host disease or recieving treatment for graft-vs-host disease. 9.Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug. 10.History of prior malignancy except for the following: a. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before 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 nonmelanomatous skin cancer. c. Adequately treated carcinoma in situ without current evidence of disease. 11.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. 12.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. 13.Received a live virus vaccination within 28 days of first dose of study drug. 14.Known history of infection with HIV or any uncontrolled active systemic infection (eg, bacterial, viral or fungal). 15.Active cytomegalovirus (CMV) infection (active viremia as evidenced by positive polymerase chain reaction [PCR] result for CMV DNA). 16.Serologic status reflecting active hepatitis B or C infection. Subjects with anti-HBc who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are HbsAg-positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded. 17.Ongoing, drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint of the study is PFS (defined as the time from randomization until disease progression or death from any cause) as assessed by the IRC per IWCLL 2008 criteria.;Timepoint(s) of evaluation of this end point: Estimated 48 months;Main Objective: To evaluate the efficacy of acalabrutinib monotherapy (Arm A) compared with idelalisib/rituximab or bendamustine/rituximab (Arm B) based on Independent Review Committee (IRC) assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Hallek 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson 2012)—hereafter referred to as IWCLL 2008 criteria in subjects with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).;Secondary Objective: To evaluate Arm A (acalabrutinib) compared with Arm B (idelalisib/rituximab or bendamustine/rituximab) in terms of: • Investigator (INV)-assessed PFS per IWCLL 2008 criteria. • INV- and IRC-assessed overall objective response rate (ORR) per IWCLL 2008 criteria. • Overall survival (OS). • Patient-reported outcomes (PROs) by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT Fatigue). • INV- and IRC-assessed duration of response (DOR). • INV- and IRC-assessed time to next treatment (TTNT). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • INV-assessed PFS per IWCLL 2008 criteria. • INV-assessed ORR (defined as the proportion of patients who achieve a best response of complete remission [CR], complete remission with incomplete bone marrow recovery [CRi], nodal partial remission [nPR], or partial remission [PR]) per IWCLL 2008 criteria. • IRC-assessed ORR per IWCLL 2008 criteria. • OS (defined as the time from randomization to the date of death due to any cause) • PROs as measured by change in scores from baseline to each assessment in the FACIT-Fatigue. • INV- and IRC-assessed DOR (defined as the time from the first documentation of objective response to the earlier time of disease progression [assessed by the IRC per IWCLL 2008 criteria] or death from any cause) • INV- and IRC-assessed TTNT (defined as the time from randomization to institution of nonprotocol-specified treatment for CLL) ;Timepoint(s) of evaluation of this end point: Estimated 48 months | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Poland, Romania, Russian Federation, Singapore, Slovakia, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactMedical Director
Acerta Pharma
Outcome results
None listed