Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacodynamics of Entospletinib in Adults With Relapsed or Refractory Hematologic Malignancies
Condition: Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Diffuse Large B-cell Lymphoma; Non-FL Indolent Non-Hodgkin's Lymphoma; Follicular Lymphoma
MeSH terms: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms
Intervention: Entospletinib MM; Entospletinib SDD
Intervention description: Entospletinib MM tablet administered orally; Entospletinib SDD tablet administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 326.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SYK inhibitor

Summary:

      The primary objective of the study is to evaluate efficacy of entospletinib in participants
      with relapsed or refractory hematologic malignancies. Participants with the following
      relapsed or refractory hematologic malignancies will be enrolled into the study: relapsed or
      refractory chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large
      B-cell lymphoma (DLBCL), follicular lymphoma (FL), or non-FL indolent non-Hodgkin lymphomas
      (iNHL; including lymphoplasmacytoid lymphoma/ Waldenström macroglobulinemia [LPL/WM], small
      lymphocytic lymphoma [SLL], or marginal zone lymphoma [MZL]).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Diagnosis of B-cell iNHL, DLBCL, MCL, or 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®)
             ; individuals with malignancies being studied in these protocols must have failed
             screening in the respective idelalisib protocol

          -  Prior treatment for lymphoid malignancy requiring treatment for progressive disease

          -  Presence of radiographically measurable lymphadenopathy or extranodal lymphoid
             malignancy

          -  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
             non-Hodgkin lymphoma (ie, Richter transformation) except if the CLL participant is
             enrolling in the BCR previously treated cohort

          -  Known active central nervous system or leptomeningeal lymphoma

          -  Presence of known intermediate- or high-grade myelodysplastic syndrome

          -  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.