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

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).

Sex

All

Minimum age

18 Years

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.

• RESULTBarrientos JC, Coutre SE, de Vos S, et al. Long-term follow-up of a Phase 1b trial of idelalisib in combination with chemoimmunotherapy in patients with relapsed/refractory chronic lymphocytic leukemia including patients with del17p/TP53 mutation. 51st Annual Meeting of the American Society of Clinical Oncology (ASCO). 29 May-02 June 2015; Chicago, IL, USA. [Poster 7011].
• RESULTBarrientos J, Coutre S, de Vos S, et al. Long-term follow-up of a Phase 1 study evaluating the selective PI3K-delta inhibitor idelalisib in combination with bendamustine (B), bendamustine/rituximab (BR), fludarabine (F), chlorambucil (Chl), Or chlorambucil/rituximab (ChlR) in patients with relapsed or refractory chronic lymphocytic leukemia. Society of Hematology (ASH) Annual Meeting. December 6-9, 2014; San Francisco, CA, USA. Poster 3343.
• RESULTde Vos S, Wagner-Johnston N, Coutre S, et al. Durable responses following treatment with the PI3K-delta inhibitor idelalisib in combination with rituximab, bendamustine, or both, in recurrent indolent non-Hodgkin lymphoma: Phase I/II results. Society of Hematology (ASH) Annual Meeting. December 6-9, 2014; San Francisco, CA, USA. Poster 3063.
• RESULTBarrientos J, Leonard J, Furman R, Flinn I, De Vos S, Coutre S, et al. Phase 1b study of idelalisib (GS-1101) plus chlorambucil ± rituximab in patients with relapsed and refractory chronic lymphocytic leukemia (CLL). European Hematology Association (EHA) 2013 Congress, 13-16 June 2013; Stockholm, Sweden. Abstract P100.
• RESULTBarrientos J, Sharman J, De Vos S, et al. GS-1101 (CAL-101), selective phosphatidylinositol 3-Kinase inhibitor, in combination with ofatumumab for treatment of relapsed/refractory chronic lymphocytic leukemia. European Hematology Association (EHA) 2012 Congress, 14-17 June 2012; Amsterdam, The Netherlands. Abstract 1062.
• RESULTCoutre S, Leonard J, Furman R, et al. Combinations of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor GS-1101 (CAL-101) with rituximab and/or bendamustine are tolerable and highly active in patients with relapsed or refractory chronic lymphocytic leukemia (CLL): results from a phase 1 study. American Society of Hematology (ASH) Annual Meeting. 8-11 December 2012; Atlanta, GA, USA. Abstract 642.
• de Vos S, Schreeder M, Finn I, et al. A phase 1 study of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). American Society of Hematology (ASH) 2011 Annual Meeting, 10-13 December 2011; San Diego, CA, USA. Abstract 2699.