Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Idelalisib; Chlorambucil; Obinutuzumab
Intervention description: 150 mg tablet administered orally twice daily; 2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses; 1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
Intervention MeSH terms: Obinutuzumab; Idelalisib; Chlorambucil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Safety Run-In Phase: Single Group; Randomized Phase: Parallel
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the effects of idelalisib with
      obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free
      survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).

      An increased rate of deaths and serious adverse events (SAEs) among participants with
      front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in
      combination with standard therapies was observed by the independent data monitoring committee
      (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data
      and terminated those studies in agreement with the DMC recommendation and in consultation
      with the US Food and Drug Administration (FDA). All front-line studies of idelalisib,
      including this study, were also terminated.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Not a candidate for fludarabine therapy based on either:

               1. creatinine clearance < 70 mL/min, or

               2. Cumulative Illness Rating Scale score > 6, by assessment of the investigator

          -  Diagnosis of B-cell CLL, with diagnosis established according to International
             Workshop on Chronic Lymphocytic Leukemia (IWCLL)

          -  No prior therapy for CLL other than corticosteroids for disease complications.

          -  CLL that warrants treatment

          -  Presence of measurable lymphadenopathy

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

        Key Exclusion Criteria:

          -  Known histological transformation from CLL to an aggressive lymphoma (ie, Richter
             transformation)

          -  Known presence of myelodysplastic syndrome

          -  Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
             randomization

          -  Ongoing liver injury

          -  Ongoing drug-induced pneumonitis

          -  Ongoing inflammatory bowel disease

          -  History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

          -  Ongoing immunosuppressive therapy other than corticosteroids

          -  Concurrent participation in another therapeutic clinical trial

          -  Undergone major surgery within 30 days prior to randomization

          -  Known hypersensitivity or intolerance to any of the active substances or excipients in
             the formulations for idelalisib, obinutuzumab, or chlorambucil

          -  History of non-infectious pneumonitis

          -  Received last dose of study drug on another therapeutic clinical trial within 30 days
             prior to randomization

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.