Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Avelumab; Utomilumab; Rituximab; Azacitidine; Bendamustine; Gemcitabine; Oxaliplatin
Intervention description: Investigational fully human anti-PD-L1 monoclonal antibody; Investigational, fully human IgG2 CD 137/4-1BB agonist; CD20-directed cytolytic antibody; Antimetabolite antineoplastic agent and demethylation agent.; Alkylating drug; Nucleoside analogue; Platinum-based drug
Intervention MeSH terms: Rituximab; Avelumab; Gemcitabine; Oxaliplatin; Azacitidine; Bendamustine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Study B9991011 is a multi-center, international, randomized, open label, 2 component (Phase
      1b followed by Phase 3), parallel-arm study of avelumab in combination with various agents
      for the treatment of Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL).
    

Eligibility criteria:

        Key Inclusion Criteria:

        -Any of the following as defined by the WHO, 2016 lymphoid neoplasm classifications and
        histologically confirmed:

          -  Diffuse large B-cell lymphoma (DLBCL), Not Otherwise Specified (NOS): Germinal center
             B-cell type (GCB), Activated B-cell type (ABC)

          -  High-grade B-cell lymphoma (HGBCL) NOS

          -  HGBCL with MYC and BCL2 and/or BCL6 rearrangements

          -  T-cell histocyte-rich large B-cell lymphoma

          -  EBV+ DLBCL, NOS

          -  HHV8+ DLBCL, NOS

        Relapsed or refractory disease following at least 2 lines (and a maximum of 4 lines) of
        prior rituximab containing multi-agent chemotherapy which may include an autologous stem
        cell transplantation unless patients are not considered suitable for intensive second-line
        chemotherapy or autologous stem cell transplantation. Patients who are ineligible for
        intensive second line chemotherapy,must have received at least one prior
        rituximab-containing combination chemotherapy regimen. Patients who are ineligible for
        intensive second line chemotherapy, must have received at least one prior
        rituximab-containing combination chemotherapy regimen.

          -  Baseline measurable disease with at least 1 bi dimensional lesion with longest
             diameter (LDi) >1.5cm on CT scan which is FDG avid on PET scan.

          -  A biopsy (archived or Screening/recent) will be collected at Screening.

          -  At least 18years of age (or ≥20 years in Japan).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

        Key Exclusion Criteria:

          -  Active central nervous system (CNS) lymphoma.

          -  Prior organ transplantation including prior allogeneic SCT.

          -  Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic
             T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab,
             tremelimumab or any other antibody, or drug specifically targeting T cell co
             stimulatory or immune checkpoint pathways).