Ensayos clínicos

Inclusion Criteria

• Diagnosis of B-cell CLL, established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and having received at least 2 prior treatment regimens
• CLL that warrants treatment
• Clinically quantifiable disease burden defined as
  • For Phase Ib
    • Absolute lymphocyte count (ALC) > 5000/μL in peripheral blood
  • For Phase II 
    • At least 1 node ≥ 2 cm on computed tomography (CT) or magnetic resonance imaging (MRI)
    • Or bone marrow exam is performed at screening and demonstrates quantifiable CLL
• Discontinuation of
  • All cytotoxic chemotherapy and anti-CD20 antibody therapy for ≥ 4 weeks
  • Alemtuzumab for ≥ 8 weeks
  • Targeted therapy for ≥ 2 weeks
  • Investigational therapy for ≥ 3 weeks before enrollment (Phase 1b) or randomization (Phase 2)
    • For relapsed CLL most recently treated with B-cell receptor (BCR) pathway inhibitors which, in the opinion of the investigator, will not tolerate waiting 3 weeks, a washout period of > 5 half-lives is allowed
    • If on a systemic corticosteroid, the dose must be stable for the previous 4 weeks
• Eastern Cooperative Oncology Group (ECOG) score of ≤ 2

Exclusion Criteria

• Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
• Known presence of myelodysplastic syndrome
• History of a non-CLL malignancy except for the following
  • Adequately treated local basal cell or squamous cell carcinoma of the skin
  • Cervical carcinoma in situ
  • Superficial bladder cancer
  • Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to enrollment
  • Other adequately treated Stage 1 or 2 cancer currently in complete remission
  • Any other cancer that has been in complete remission for ≥ 2 years
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
• Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension
• History of drug-induced pneumonitis
• Ongoing inflammatory bowel disease
• Ongoing alcohol or drug addiction
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
• Ongoing systemic immunosuppressive therapy other than corticosteroids
• History of prior therapy with any phosphatidylinositol 3-kinase (PI3K) inhibitor (including idelalisib), or any anti-CD37 agent
• Ongoing infection with, or treatment or prophylaxis for, CMV within the past 28 days