Phase II Trial of Alemtuzumab (Campath) and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in Relapsed or Refractory Diffuse Large B-Cell and Hodgkin Lymphomas

Background: Two signatures of the microenvironment were recently identified that are predictive of outcome in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine (Oncovin) and prednisone (R-CHOP). These signatures, called stromal 1 and stromal 2, are associated with genes expressed by infiltrating mononuclear cells. The stromal 2 signature, which includes genes associated with angiogenesis, is predictive of an inferior outcome. Based on these observations, we are interested in targeting the reactive cells in the microenvironment as a therapeutic strategy in patients with relapsed and refractory DLBCL. Along the same principles, we are also including patients with relapsed Hodgkin lymphoma (HL). The surrounding reactive cells around Hodgkin Reed Sternberg (HRS) cells are now not thought to be bystander cells and they appear to provide important survival signals to HRS cells. * Campath-1 antigen (CD52) is one such promising target that is highly expressed in most of these infiltrating cells and on most DLBCL although not on HRS cells specifically. Anti-CD52 antibodies may have therapeutic value by depleting reactive B and T cells, and monocytes from the microenvironment. * The dose of alemtuzumab in combination with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH) is 30 mg intravenous (IV), as determined by a prior study done in patients with untreated peripheral T-cell lymphoma. The main toxicities of this combination are myelosuppression and opportunistic infections. * An important component of this study will be to obtain tumor tissue for gene expression profiling and to assess microenvironment signatures and look at other molecular signatures and targets before treatment and in patients who progress and ultimately correlate response and outcome with these various end-points. Objectives: \- Assess response, progression free survival (PFS) and overall survival (OS) in relapsed/refractory DLBCL and Hodgkin Lymphoma. Eligibility: * Previously treated or refractory classical large B-cell lymphomas, Grey-zone lymphoma and Hodgkin lymphoma, including Lymphocyte predominant Hodgkin Lymphoma (LPHL). * Age greater than or equal to 18 years with adequate organ functions. * Human immunodeficiency virus (HIV) negative and no active central nervous system (CNS) lymphoma. Study Design: * Patients will receive 30mg of Alemtuzumab on day 1 of therapy, followed by Rituximab on day 1 and dose-adjusted EPOCH chemotherapy days 1-5, up to six cycles of therapy. * Tumor biopsies will be done before treatment, after 1 cycle of therapy and at relapse. * It is anticipated that up to 10-15 patients per year may be enrolled onto this trial. Thus, accrual of up to 52 patients is expected to require approximately 4-5 years.