Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies
Condition: Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Diffuse Large B-cell Lymphoma; Indolent Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms
Intervention: Entospletinib; Idelalisib
Intervention description: Entospletinib tablets administered orally twice daily; Idelalisib tablets administered orally twice daily
Intervention MeSH terms: Idelalisib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GS-US-339-0103; SYK inhibitor; PI3K inhibitor; GS-9973; GS 9973; GS-1101; GS 1101; Cal-101; Cal 101; idelalisib; leukemia; lymphoma; CLL; MCL; DLBCL; iNHL; FL; MZL; LPL; SLL; WM; Waldenström's macroglobulinemia

Summary:

      This study will evaluate the efficacy of the combination entospletinib and idelalisib in
      participants with relapsed or refractory hematologic malignancies. Participants will be
      enrolled who have one of the following hematological tumor types: chronic lymphocytic
      leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), or
      indolent non-Hodgkin lymphomas (iNHL; including follicular lymphoma (FL) and
      lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia [LPL/WM], small lymphocytic
      lymphoma [SLL], or marginal zone lymphoma [MZL]).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosis of B-cell indolent non-Hodgkin lymphoma (iNHL),diffuse large B-cell lymphoma
             (DLBCL),mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) as
             documented by medical records and with histology based on criteria established by the
             World Health Organization

          -  For institutions that have Phase 3 or Phase 4 protocols studying idelalisib (Zydelig®;
             GS-1101); individuals with malignancies being studied in these protocols must have
             failed screening and be registered as a screen failure in the respective idelalisib
             protocol

          -  Prior treatment for lymphoid malignancy

          -  Presence of radiographically measurable lymphadenopathy or extranodal lymphoid
             malignancy

          -  Discontinuation of all therapy for the treatment of cancer ≥ 3 weeks before the start
             of study drug

          -  All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before
             the start of study drug

          -  Karnofsky performance status of ≥ 60

          -  Life expectancy of at least 3 months

        Key Exclusion Criteria:

          -  Known histological transformation from iNHL or CLL to an aggressive form of NHL (ie,
             Richter transformation)

          -  Known active central nervous system or leptomeningeal lymphoma

          -  Presence of known intermediate- or high-grade myelodysplastic syndrome

          -  Current therapy with agents that reduce gastric acidity, including but not limited to
             antacids, H2 inhibitors, and proton pump inhibitors

          -  Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of
             start of study drug

          -  Ongoing liver injury

          -  Ongoing or recent hepatic encephalopathy

          -  Ongoing drug-induced pneumonitis

          -  Ongoing inflammatory bowel disease

          -  Ongoing alcohol or drug addiction

          -  Pregnancy or breastfeeding

          -  History of prior allogeneic bone marrow progenitor cell or solid organ transplantation

          -  Ongoing immunosuppressive therapy

          -  Concurrent participation in an investigational drug trial with therapeutic intent

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.