A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL

A Phase 2 Single Arm Study to Investigate the Safety and Clinical Activity of Idelalisib Alone and in Combination With Rituximab in Elderly Subjects With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is to evaluate the safety and clinical activity of idelalisib alone and in combination with rituximab in patients with CLL or SLL.

This Phase 2 study will be the first time that idelalisib is administered to previously untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity, which supports its evaluation in previously untreated patients. The study population is limited to patients over 65 years of age because younger patients are generally appropriate for standard immunochemotherapy regimens that are highly active. Since the mechanism of action of idelalisib is distinct from rituximab, it is hypothesized that the combination will be more active than either agent alone. This study will establish initial safety and clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL. Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in subjects with untreated CLL or SLL.

Key Inclusion Criteria:

• Histologically or cytologically confirmed CLL or SLL.

• Age ≥ 65

• Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥ 1.5 cm in the longest diameter (LD) and ≥ 1.0 cm in the longest perpendicular diameter (LPD) as assessed by physical exam, computed tomography (CT) or magnetic resonance imaging (MRI)).

• CLL - Binet Stage C or Rai Stage III or IV or has active disease defined by meeting at least one of the following criteria:

  • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

  • Massive (ie, > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly

  • Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy

  • Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than 6 months

  • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy

  • At least one of the following disease-related symptoms:

    • Unintentional weight loss ≥ 10% within the previous 6 months
    • Significant fatigue
    • Fevers > 100.4 F for ≥ 2 weeks without other evidence of infection
    • Night sweats for ≥ 1 month without evidence of infection

• SLL - has active disease as defined above for CLL, except the lymphocytosis criterion does not apply

• World Health Organization (WHO) Performance Status of ≤ 2

• For men of child-bearing potential, willing to use adequate methods of contraception for the entire duration of the study

• Able to provide written informed consent

Key Exclusion Criteria:

• Prior therapy for CLL or SLL, except corticosteroids for symptom relief
• Treatment with a short course of corticosteroids for symptom relief within 1-week prior to Visit 1
• Known active central nervous system involvement of the malignancy
• Ongoing active, serious infection requiring systemic therapy. Patients may be receiving prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
• Serum creatinine ≥ 2.0 mg/dL
• Serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) or serum transaminases (ie, aspartate aminotransferase (AST), alanine aminotransferase (ALT)) ≥ 2 x upper limit of normal
• Positive test for human immunodeficiency virus (HIV) antibodies
• Active hepatitis B or C (confirmed by ribonucleic acid (RNA) test). Patients with serologic evidence of prior exposure are eligible.
• 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 study entry, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.