A Phase I/II Trial of Vorinostat (SAHA) (NSC-701852) in Combination with Rituximab-CHOP in Patients with Newly Diagnosed Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL)

Patients must have biopsy proven, newly diagnosed Diffuse Large B-Cell Lymphoma
(DLBCL) with Stage II bulky, Stage III or Stage IV disease, with an IPI or R-IPI score greater than 0 (see Section 4.0). A report providing confirmation of CD20 expression must be submitted per Section 14.4. Pathology review: Adequate sections from the original diagnostic specimen must be available for submission for review by the SWOG Lymphoma Pathology Laboratory as outlined in Section 12.0. An adequate biopsy requires sufficient tissue to establish the architecture and WHO histologic subtype with certainty. Fine needle aspiration or cytology is not adequate. Patients must be offered the opportunity to consent to the correlative science studies. Patients are encouraged to submit specimens for correlative studies as outlined in Section 15.0; however, specimen submission is not a requirement for participation in the study. Patients must have measurable disease (see Section 10.0). Measurable disease must be determined by CT scan of chest, abdomen and pelvis performed within 28 days prior to registration. CT reports must be submitted per Section 14.4. PET/CT may be substituted for CT scan only if CT scan is of diagnostic quality and is contrast enhanced. Patients must be >/=18 years of age. Patients must have a unilateral bone marrow aspirate and biopsy for staging performed within 42 days prior to registration. Patients must not have clinical evidence of central nervous system involvement by lymphoma. Any laboratory or radiographic tests performed within 42 days prior to registration to assess CNS involvement must be negative. Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma. Steroid pre-medication for IV contrast allergy is allowed. Patients must have Zubrod performance status of 0-2 (see Section 10.4). Patients must have serum LDH measured within 28 days prior to registration. Patients must have an ANC > 1,000/mcL and platelets > 100,000/mcL within 28 days prior to registration, unless due to bone marrow infiltration by lymphoma. Patients must have a cardiac ejection fraction �� institutional lower limit of normal (ILLN) by MUGA scan or 2-D ECHO with no significant abnormalities within 42 days prior to registration. Patients must not have received valproic acid (a HDAC inhibitor) within 28 days prior to registration. Patients must have no known hypersensitivity to the components of treatment. Patients must be willing to discontinue taking any medications that are generally accepted to have a risk of causing Torsades de Pointes while on study(http://torsades.org). Patients known to be HIV positive are not eligible. Existing therapeutic options are effective and study design does not support assessing the efficacy of treatment on those with HIV. No other 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 from which the patient has been disease free for five years. Pregnant or nursing women must not participate due to potential for congenital abnormalities, and of harm to nursing infants due to this treatment regimen. Women and men of reproductive potential must not participate unless they have agreed to use an effective contraceptive method. All 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.