This is a study to test how safe the combination of the drugs Romidepsin and Pralatrexate are in patients with lymphoid malignancies and to determine the dose of the combination of drugs that is safest. If the combination is determined to be safe, the study will continue accrual patients with peripheral T-Cell lymphoma (PTCL).

The non- Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies. Under the rubric of lymphoma exist some of the fastest growing cancers known to science, (Burkett's lymphoma, lymphoblastic lymphoma/leukemia), as well as some of the most indolent (small lymphocytic lymphoma, follicular lymphoma, and marginal zone lymphoma). This remarkable diversity of biology imposes significant challenges. Researchers are seeking to understand the cell of origin and differentiate what are sometimes subtle differences between the related sub-types of disease; and to identify the best treatments for these subtypes, with the ever-increasing likelihood that new understanding of the molecular pathogenesis of these diseases will result in an increase in new drugs for specific target populations.

Inclusion Criteria:

Phase I: Patients must have histologically confirmed relapsed or refractory Non-Hodgkin's lymphoma, Hodgkin's Disease or multiple myeloma (defined by World Health Organization (WHO) criteria).

Phase II: Patients must have histologically confirmed relapsed or refractory T-Cell Lymphoma (as defined by WHO criteria).

• Must have received first line chemotherapy. No upper limit for the number of prior therapies
• Evaluable Disease
• Age ≥18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Patients must have adequate organ and marrow function as defined in the protocol
• Adequate Contraception
• Ability to understand and the willingness to sign a written informed consent document
• Inclusion Criteria for Multiple Myeloma patients specified in the protocol

Exclusion Criteria:

• Prior Therapy

  • Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
  • Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
  • No other investigational agents are allowed

• Central nervous system metastases, including lymphomatous meningitis

• History of allergic reactions to Pralatrexate or Romidepsin

• Uncontrolled intercurrent illness

• Pregnant women

• Nursing women

• Current malignancy or history of a prior malignancy, as outlined in the protocol

• Patient known to be Human Immunodeficiency Virus (HIV)-positive

• Active Hepatitis A, Hepatitis B, or Hepatitis C infection