Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Condition: Indolent Non-Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell
Intervention: Idelalisib; Rituximab; Bendamustine; Ofatumumab; Fludarabine; Everolimus; Bortezomib; Chlorambucil; Lenalidomide
Intervention description: Idelalisib tablet administered orally; Rituximab administered intravenously; Bendamustine administered intravenously; Ofatumumab administered intravenously; Fludarabine administered orally; Everolimus administered orally twice daily until disease progression; Bortezomib administered as a subcutaneous injection; Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.; Lenalidomide administered orally
Intervention MeSH terms: Rituximab; Fludarabine; Lenalidomide; Everolimus; Bortezomib; Bendamustine Hydrochloride; Ofatumumab; Idelalisib; Chlorambucil
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 241.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: phosphatidylinositol 3-kinase; Ofatumumab; indolent non-Hodgkin lymphoma (iNHL)

Summary:

      The primary objective of the study is to evaluate the safety of idelalisib in combination
      with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of
      rapamycin (mTOR) inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an
      immunomodulatory agent in participants with relapsed or refractory indolent B-cell
      non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia
      (CLL).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Age ≥ 18

          -  Previously treated with relapsed or refractory disease (refractory defined as not
             responding to a standard regimen or progressing within 6 months of the last course of
             a standard regimen)

          -  Disease status requirement:

               -  For CLL patients, symptomatic disease that mandates treatment as defined by the
                  International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria

               -  For indolent NHL and MCL patients, measurable disease by CT scan defined as at
                  least 1 lesion that measures > 2 cm in a single dimension

          -  WHO performance status of ≤ 2

          -  For men and women of child-bearing potential, willing to use adequate contraception
             (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration
             of the study.

               -  For Cohort 7 only: Women of child bearing potential must have 2 negative
                  pregnancy tests prior to starting lenalidomide.

          -  Able to provide written informed consent

        Key Exclusion Criteria:

          -  Is not a good candidate to receive any of the drugs administered in the study for a
             given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine,
             everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the
             investigator

          -  Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1
             over-expression (CLL patients only)

          -  Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment
             with an investigational product within 4-weeks prior to the baseline disease status
             tests

          -  Had treatment with a short course of corticosteroids for symptom relief within 1-week
             prior to the baseline disease status tests

          -  Has had an allogeneic hematopoietic stem cell transplant

          -  Has known active central nervous system involvement of the malignancy

          -  Is pregnant or nursing

          -  Has active, serious infection requiring systemic therapy. Patients may receive
             prophylactic antibiotics and antiviral therapy at the discretion of the investigator

          -  Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL,
             MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by
             tumor cells

          -  Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL,
             the latter documented by > 50% infiltration of bone marrow by tumor cells

          -  Has serum creatinine ≥ 2.0 mg/dL

               -  For Cohort 7 only: Has creatinine clearance < 60 mL/min

          -  Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with
             iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal

          -  Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper
             limit of normal

          -  Has Child-Pugh Class B or C hepatic impairment

          -  Has a positive test for HIV antibodies

          -  Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence
             of prior exposure are eligible.

          -  Prior treatment with idelalisib

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.