Bendamustine, Obinutuzumab, and Dexamethasone in Older Patients With Diffuse Large B-cell Lymphoma
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Bendamustine Hydrochloride; Obinutuzumab; Dexamethasone; Quality-of-Life Assessment; Laboratory Biomarker Analysis
Intervention description: Given IV; Given IV; Given PO; Ancillary studies; Correlative studies
Intervention MeSH terms: Dexamethasone; Bendamustine Hydrochloride; Obinutuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well bendamustine hydrochloride, obinutuzumab, and
      dexamethasone work in treating older patients with diffuse large B-cell lymphoma. Drugs used
      in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways
      to stop the growth of cancer cells, either by killing the cells, by stopping them from
      dividing, or by stopping them from spreading. Monoclonal antibodies, such as obinutuzumab,
      may find cancer cells and help kill them. Giving bendamustine hydrochloride, obinutuzumab,
      and dexamethasone may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed DLBCL, cluster of differentiation (CD)20 positive by flow or
             immunohistochemistry (IHC); transformed DLBCL is allowed as long as no prior therapy
             has been given

          -  No prior therapy for DLBCL, except =< 1 week of corticosteroids given on an emergent
             basis or as a temporizing measure (pre-phase where indicated by the treating
             physician)

          -  Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI),
             and/or positron emission tomography (PET) with at least one target lesion measuring
             1.5 cm or larger

          -  Patients must be considered ineligible for rituximab, cyclophosphamide, doxorubicin
             hydrochloride, vincristine sulfate and prednisone (R-CHOP) standard therapy; to be
             ineligible for R-CHOP, patients must meet at least one of the following criteria are
             met:

               -  Prior anthracycline therapy for other malignancies or other disorders whereby if
                  additional anthracyclines are given for DLBCL, the maximum lifetime allowable
                  dose will be exceeded

               -  Meeting the geriatric criteria of ineligibility for standard R-CHOP if one of the
                  following criteria is present:

                    -  Three or more organ systems with a score of 3 or any 1 organ system with a
                       score of 4 (using the Cumulative Illness Rating Scale for Geriatrics,
                       [CIRS-G])

                    -  Score of 3 or above on the Vulnerable Elders Survey (VES-13)

                    -  Score of =< 9 in the short physical performance battery (SPPB)

                    -  Presence of a significant geriatric syndrome (dementia, delirium, falls,
                       incontinence, malnutrition, and severe osteoporosis) in the past year prior
                       to diagnosis

                    -  Any abnormality in performing activities of daily living (ADLs) or
                       instrumental activities of daily living (IADLs)

          -  Absolute neutrophil count (ANC) >= 1.5 unless cytopenias are related to bone marrow
             involvement with disease

          -  Hemoglobin >= 7 g/dl unless cytopenias are related to bone marrow involvement with
             disease

          -  Platelets >= 75,000 unless cytopenias are related to bone marrow involvement with
             disease

          -  Glomerular filtration rate (GFR) > 30 using Cockcroft-Gault formula

          -  Total bilirubin =< 3 times the upper limit of normal unless hepatic dysfunction is
             related to liver involvement with disease

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5.0 times the
             upper limit of normal unless hepatic dysfunction is related to liver involvement with
             disease

          -  Alkaline phosphatase =< 5.0 times the upper limit of normal unless hepatic dysfunction
             is related to liver involvement with disease

          -  The ability to understand and sign a written informed consent

        Exclusion Criteria:

          -  Prior therapy for DLBCL

          -  Other non-Hodgkin lymphoma (NHL) histologies

          -  Known central nervous system (CNS) involvement

          -  Known human immunodeficiency virus (HIV) or human T-lymphotropic virus, type I
             (HTLV-I) positive status

          -  Subjects who have current active hepatic or biliary disease (with exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL
             or stable chronic liver disease per treating investigator assessment)

          -  Treatment with any known non-marketed drug substance or experimental therapy within 4
             weeks prior to enrollment, or currently participating in any other interventional
             clinical study for NHL or any other illness (except observational and registry trials)

          -  Other past or current malignancy; subjects who have been free of malignancy for at
             least 3 years, or have a history of completely resected non-melanoma skin cancer, or
             successfully treated in situ carcinoma (any site) are eligible; women with a history
             of cervical cancers are allowed

          -  Chronic or current infectious disease requiring systemic antibiotics, antifungal
             (excluding antifungals given for nail-beds infections), or antiviral treatment such
             as, but not limited to, chronic renal infection, chronic chest infection with
             bronchiectasis, tuberculosis and active hepatitis C

          -  History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae

          -  Positive hepatitis serology:

               -  Hepatitis B virus (HBV): patients with positive serology for hepatitis B defined
                  as positivity for hepatitis B surface antigen (HBsAg) or anti-hepatitis B core
                  antibody (HBc); patients who are positive for anti-HBc may be considered for
                  inclusion in the study on a case-by-case basis if they are hepatitis B viral
                  deoxyribonucleic acid (DNA) negative and are willing to undergo ongoing HBV DNA
                  testing by real-time polymerase chain reaction (PCR); patients with positive
                  serology may be referred to a hepatologist or gastroenterologist for appropriate
                  monitoring and management

               -  Hepatitis C (hepatitis C virus [HCV]): patients with positive hepatitis C
                  serology unless HCV ribonucleic acid (RNA) is confirmed negative and may be
                  considered for inclusion in the study on a case-by-case basis

          -  Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C
             antibody (HCAb)

          -  Inability to comply with study or follow-up testing and procedures

          -  Prior radiotherapy is allowed if it was given for low-grade lymphoma before
             transformation in those with transformed NHL and as long as no chemotherapy was
             administered in conjunction with radiation

          -  Any patient receiving a live vaccine must allow a 4-week interval before starting
             treatment on this study

          -  Known hypersensitivity to mannitol

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or
             a known hypersensitivity to any of the other study drugs

          -  Major surgery within 4 weeks from cycle # 1

          -  Fertile men or women of childbearing potential unless 1) surgically sterile or 2)
             using an adequate measure of contraception such as oral contraceptives, intrauterine
             device, or barrier method of contraception in conjunction with spermicidal jelly

          -  Effective contraception is required while receiving obinutuzumab; for women, effective
             contraception is required to continue for >= 12 months after the last dose of
             obinutuzumab; for men, effective contraception is required to continue for 3 months
             after the last dose of obinutuzumab treatment

          -  Vaccination with a live vaccine a minimum of 28 days prior to the start of treatment