Pidilizumab in Treating Patients With Stage III-IV Diffuse Large B-Cell Lymphoma Following First Remission
Condition: Stage III Diffuse Large B-Cell Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Laboratory Biomarker Analysis; Pidilizumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Pidilizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate pidilizumab and its effect, bad and/or good, on the
      immune system in relation to its ability to fight cancer cells. Many cancers can be brought
      to a phase called complete remission (no cancer is found) but have a chance that they may
      come back. Researchers are working to improve therapy and to find new drugs that lower the
      chance of disease coming back. This study uses a drug called pidilizumab. The drug targets
      our immune system. It can change how our immune system finds cancer cells. The drug may kill
      any remaining cancer cells that we cannot see with computed tomography (CT) scans. The drug,
      pidilizumab, is being studied in other cancers.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed de novo DLBCL by the 4th edition of the World Health
             Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues
             published in 2008; patients with transform lymphoma are excluded; patients with known
             primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; patients with known
             c-v-myc avian myelocytomatosis viral oncogene homolog (c-myc) translocation (by
             fluorescence in situ hybridization) positive DLBCL are eligible for enrollment; c-myc
             testing prior to study enrollment is not required; availability of diagnostic biopsy
             samples in encouraged for the exploratory analysis but not required for enrollment;
             patients with "double-hit" or "triple-hit" lymphoma are eligible for enrollment

          -  Previously completed anthracycline-based induction chemotherapy with standard regimens
             including rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate,
             and prednisone (R-CHOP), dose adjusted (DA)-etoposide, prednisone, vincristine
             sulfate, doxorubicin hydrochloride, cyclophosphamide (EPOCH), and rituximab (R), and
             R-hyper cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride,
             dexamethasone, methotrexate, and cytarabine (CVAD); patients need a minimum of 6
             cycles of treatment; initial treatment with pidilizumab must be administered between
             30-90 days from last dose of induction chemotherapy

          -  Complete remission (CR) according to the Revised Response Criteria for Malignant
             Lymphoma after first-line treatment

               -  Diagnostic CT scans with contrast of chest, abdomen, and pelvis must have been
                  performed within 8 weeks from the first day of the last cycle of R-chemotherapy;
                  a neck CT will be required if the patient had involvement of the neck region at
                  initial diagnosis

               -  A negative fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT scan
                  performed within 8 weeks from the first day of the last cycle of R-chemotherapy
                  and confirming CR, with negative defined as a score of 1-3 on the Deauville
                  5-point scale used to quantify radionucleotide density in PET scans as determined
                  locally; PET positive/indeterminate lesions which are confirmed on biopsy to
                  harbor no active lymphoma will be considered negative for determination of CR
                  status

               -  If positive bone marrow involvement at initial diagnosis the patient must have a
                  negative bone marrow biopsy following R-chemotherapy to confirm the CR

          -  Stage III/IV disease by Ann Arbor Staging

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Any National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI)
             score; a calculated score required for enrollment

          -  Absolute neutrophil count (ANC) >= 1000

          -  Platelet count >= 50,000

          -  Total bilirubin =< 2 x upper limit of normal (ULN) or if total bilirubin is > 2 x ULN,
             the direct bilirubin must be normal

          -  Alkaline (Alk.) phosphatase =< 3 x ULN

          -  Aspartate aminotransferase (AST) =< 3 x ULN

          -  Creatinine =< 2 x ULN or creatinine clearance (CrCl) > 30 ml/min

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test at enrollment; FCBP must either commit to abstinence from heterosexual
             intercourse or commit to the use of 2 acceptable methods of birth control; a FCBP is
             any woman, regardless of sexual orientation or whether they have undergone tubal
             ligation, who meets the following criteria: 1) has not undergone a hysterectomy or
             bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
             consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
             months)

          -  Men must agree to use a latex condom during sexual contact with a FCBP even if they
             have had a successful vasectomy

          -  All subjects must have given signed, informed consent prior to registration on study

        Exclusion Criteria:

          -  Active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy;
             exceptions to this are as follows: localized nonmelanotic skin cancer and any cancer
             that in the judgment of the investigator has been treated with curative intent and
             will not interfere with the study treatment plan and response assessment

          -  Known central nervous system (CNS) involvement

          -  Prior stem cell transplantation (autologous or allogeneic)

          -  Persistent diarrhea or malabsorption > National Cancer Institute (NCI) Common
             Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management

          -  Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of
             immunomodulatory agents

          -  Any cancer directed therapies between completion of induction chemotherapy and
             treatment on protocol

          -  Known hypersensitivity to murine or chimeric antibodies or proteins

          -  Presence of co-morbid systemic illnesses or other severe concurrent disease which, in
             the judgment of the investigator, would make the patient inappropriate for entry into
             this study or interfere significantly with the proper assessment of safety and
             toxicity of the prescribed regimens; this includes, but not limited to, ongoing or
             active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Subjects with known human immunodeficiency virus (HIV) infection

          -  Subjects with known active hepatitis B virus (HBV) and hepatitis C virus (HCV)
             infection

          -  Women must not be pregnant or breast-feeding

          -  Unwillingness or inability to comply with the protocol