Vorinostat and Pegylated Liposomal Doxorubicin in Relapsed or Refractory Lymphomas

Exclusion Criteria

• •Patients with previously untreated lymphoma
• •Patient who has had chemotherapy, radiotherapy, or biological therapy within 3 weeks prior to initial dosing with study drugs or who has not recovered from adverse events due to agents administered more than 3 weeks earlier.
• •Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs.
• •Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
• •QTc prolongation greater than 500ms
• •Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \>5 years or are considered by their physician to be at less than 30% risk of relapse.
• •Patient is on any systemic steroids that have not been stabilized during the 3 weeks prior to the start of the study drugs.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or doxorubicin.
• •History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the components of PLD.
• •Patients with active CNS metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
• •Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.
• •Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study. Pregnant women are excluded from this study because vorinostat and doxorubicin have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat or PLD, breastfeeding should be discontinued if the mother is treated with vorinostat and PLD.
• •Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.
• •Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.
• •Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.
• •HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with vorinostat.
• •Patients with known history of Hepatitis B or C are excluded.