A Randomized, Multicenter, Open-Label, 3 Arm Phase 3 Study of Obinutuzumab in Combination with Chlorambucil, ACP 196 in Combination with Obinutuzumab, and ACP-196 Monotherapy in Subjects with Previously Untreated Chronic Lymphocytic Leukemia

Phase 1

• Conditions: ntreated Chronic Lynphocytic Leukemia; MedDRA version: 18.1Level: LLTClassification code 10009310Term: CLLSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005582-73-ES
• Lead Sponsor: Acerta Pharma BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-06-15
• Last Update Posted: 8 January 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

• Men and women = 65 years of age, or > 18 and < 65 years of age provided that they meet at least one of the following criteria:
o Creatinine clearance 30 to 69 mL/min using the Cockcroft-Gault equation.
o A score higher than 6 on the Cumulative Illness Rating Scale-Geriatric (CIRS-G) (Appendix L).
• ECOG performance status of 0, 1, or 2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
o 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.
o Prolymphocytes may comprise = 55% of blood lymphocytes.
o No evidence of cyclin D1 rearrangement or BCL-1 overexpression.
• Active disease meeting = 1 of the following IWCLL 2008 criteria for requiring treatment:
o Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/µL).
o Massive (ie, = 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
o Massive nodes (ie, = 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
o Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 x 109/L (30,000/µL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
o Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
o Constitutional symptoms documented in the subject’s chart with supportive objective measures, as appropriate, defined as = 1 of the following disease-related symptoms or signs:
- Unintentional weight loss = 10% within the previous 6 months before Screening.
- Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.
- Night sweats for > 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.
• Meet the following laboratory parameters:
o Absolute neutrophil count = 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.
o 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.
o Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN).
o Total bilirubin = 2.5 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 at the institution that administers study drug for the entire study.
• Women of childbearing potential who are sexually active with a male partner must have a negative serum pr

Exclusion Criteria

• Any prior treatment for CLL.
• 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. 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.
• 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).
• 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 28 days of first dose of study drug.
• Requires treatment with long-acting proton pump inhibitor

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified