Study of Idelalisib in Combination With BI 836826 in Participants With Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia (CLL)
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Idelalisib; BI 836826
Intervention description: Tablets administered orally twice daily; Intravenous administration as a rate-controlled infusion
Intervention MeSH terms: Idelalisib; BI 836826
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 1b: sequential assignment, Phase 2: parallel assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study consists of 2 parts: Phase 1b and Phase 2. Phase 1b will evaluate the safety and
      tolerability of the combination of idelallisib with the anti-CD37 monoclonal antibody BI
      836826 in participants with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), and
      establish the high recommended Phase 2 combination dose (highRP2D) as well as an alternate
      lower recommended Phase 2 combination dose (lowRP2D). Phase 2 will determine the rates of
      complete response (CR) and of minimal residual disease (MRD) negativity with the combination
      at the highRP2D and the lowRP2D in participants with R/R CLL.
    

Eligibility criteria:

        Key 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 1b individuals: absolute lymphocyte count (ALC) > 5000/μL in peripheral
                  blood.

               -  For Phase 2 individuals either:

                    -  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, and investigational
             therapy for ≥ 3 weeks before enrollment (Phase 1b) or randomization (Phase 2). For
             individuals with relapsed CLL most recently treated with B-cell receptor (BCR) pathway
             inhibitors who, 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

        Key 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, or 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.

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.