Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma
Condition: Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse
Intervention: rituximab; bevacizumab; cyclophosphamide; doxorubicin hydrochloride; vincristine sulfate; prednisone; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given PO; Correlative studies
Intervention MeSH terms: Prednisone; Cyclophosphamide; Bevacizumab; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving combination chemotherapy together with
      rituximab and bevacizumab works in treating older patients with stage II, stage III, or stage
      IV diffuse large B-cell lymphoma. Drugs used in chemotherapy work in different ways to stop
      the growth of cancer cells, either by killing the cells or by stopping them from dividing.
      Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal
      antibodies, such as rituximab and bevacizumab, can block cancer growth in different ways.
      Some block the ability of cancer cells to grow and spread. Others find cancer cells and help
      kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of
      cancer cells by blocking blood flow to the cancer. Giving combination chemotherapy together
      with monoclonal antibodies may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All patients must have previously untreated Stage III, IV, or bulky Stage II diffuse
             large B-cell non-Hodgkin's lymphoma which is positive for CD20; a report providing
             confirmation of CD20 expression must be submitted

          -  Pathology Review: Adequate sections from the original diagnostic specimen must be
             available for submission for review by the SWOG Lymphoma Pathology Laboratory; an
             adequate biopsy requires sufficient tissue to establish the architecture and a REAL or
             WHO histologic subtype with certainty; thus, core biopsies, especially multiple core
             biopsies may be adequate; whereas, needle aspirations or cytologies are not adequate

          -  Specimens for analysis of angiogenic markers must be submitted to the University of
             Arizona

          -  All patients must have bidimensionally measurable disease documented within 28 days
             prior to registration; patients with non-measurable disease in addition to measurable
             disease must have all nonmeasurable disease assessed within 42 days prior to
             registration

          -  Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed
             within 42 days prior to registration

          -  Patients must have a CT scan of the chest/abdomen and pelvis performed within 28 days
             prior to registration

          -  Patients must not have clinical evidence of central nervous system involvement by
             lymphoma; any laboratory or radiographic tests performed to assess CNS involvement
             must be negative within 42 days of registration

          -  Patients may not have a previous diagnosis of indolent lymphoma (histologic
             transformation or mixed histologies with an indolent or nodular component are
             ineligible)

          -  Patients must not have received prior chemotherapy, radiation, or antibody-based
             therapy for lymphoma

          -  Patients must have a Zubrod performance status of 0 - 2

          -  Serum LDH must be measured within 28 days prior to registration

          -  Patients must have a cardiac ejection fraction >= 45% by MUGA scan or a 2-d ECHO with
             no significant abnormalities within 42 days prior to registration

          -  Absolute neutrophil count > 1,000/mcL obtained within 28 days prior to registration

          -  Platelet count > 100,000/mcL obtained within 28 days prior to registration

          -  Serum creatinine < 2 x the institutional upper limit of normal within 28 days prior to
             registration

          -  Patients must have urine proteinuria screened by dipstick or urine analysis within 28
             days prior to registration; in patients with proteinuria >= +1 or urine
             protein:creatinine ratio >= 1.0, a 24 hour urine protein should be obtained and the
             level < 1gm/24 hours to be eligible

          -  Patients must not have a history of hypersensitivity reaction to products containing
             Polysorbate 20 (Tween 20), Chinese hamster ovary cell products, or recombinant human
             antibodies

          -  Patients known to be HIV-positive, or who have a history of solid organ
             transplantation are ineligible due to the concern over immunosuppression associated
             with B-cell depletion; patients at high risk of Hepatitis B virus infection should be
             screened before initiation of rituximab

          -  Patients must not have uncontrolled hypertension

          -  Patients with a history of prior myocardial infarction, unstable angina, stroke, or
             arterial thrombosis within 6 months are ineligible

          -  Patients with clinically significant peripheral vascular disease, a serious or
             non-healing wound, ulcer, or bone fracture, or a bleeding diathesis/coagulopathy are
             ineligible

          -  Patients with a history of venous thrombosis requiring full-dose anticoagulation or
             currently receiving anticoagulation therapy may be eligible provided that the
             following criteria are met:

               -  The patient must have an in-range INR (usually between 2 and 3) on a stable dose
                  of warfarin or on a stable dose of LMW heparin

               -  The patient must not have bleeding or pathological conditions that carry a high
                  risk of bleeding (e.g. tumor involving major vessels, known varices)

          -  Patients who have had a major surgical procedure or traumatic injury within 28 days
             prior to registration or anticipation of major surgical procedure during the course of
             therapy are ineligible

          -  Patients with a history of abdominal fistula, gastrointestinal perforation, or
             intra-abdominal abscess within 6 months are ineligible

          -  Patients requiring continuous supplemental oxygen therapy are ineligible

          -  No prior malignancy is allowed except for the following: adequately treated basal cell
             or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or
             II cancer from which the patient is currently in complete remission, or any other
             cancer for which the patient has been disease-free for five years

          -  Pregnant or nursing women may not participate in this study due to the potential for
             congenital abnormalities, and of harm to nursing infants due to this treatment
             regimen; women or men of reproductive potential may not participate unless they have
             agreed to use an effective contraceptive method during the study period and for at
             least 6 months after the completion of therapy

          -  If Day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next
             working day

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  At the time of patient registration, the treating institution's name and ID number
             must be provided to the Data Operations Center in Seattle in order to ensure that the
             current (within 365 days) date of institutional review board approval for this study
             has been entered into the data base