The standard treatment for PTCL is CHOP (cyclophosphamide (C), adriamycin (H), vincristine (O), and prednisone (P)) chemotherapy. This study is attempting to determine whether adding other treatments to CHOP therapy will improve the chance of the disease going into remission or staying in remission. Because other drugs for T-cell lymphoma have not yet been given with CHOP, this study is looking at combining CHOP with ONTAK. ONTAK has been FDA approved for treatment of Cutaneous T cell Lymphoma and works by specifically binding to a protein on the surface of the tumor cells and killing the cell without causing damage to other types of cells in the body. Studies have shown that ONTAK has helped patients with PTCL who have failed chemotherapy.

Inclusion Criteria:

• Pathological diagnosis of peripheral T-cell lymphoma of one of following histologies as per the REAL classification: peripheral T-cell lymphoma (unspecified), anaplastic large cell lymphoma CD30+, angioimmunoblastic T-cell lymphoma, nasal/nasal type T/NK cell lymphoma, intestinal T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitic T-cell lymphoma.
• Treatment naive except for prior radiation or a single cycle of CHOP.
• Patients must have at least one clear-cut bidimensionally measurable site by physical exam and/or computed tomography. Baseline measurements of measurable sites and evaluation of evaluable disease must be obtained within 4 weeks prior to registration to this study.
• Prior radiation therapy for localized disease is allowed as long as the irradiated area is not at the mediastinal area or at the only site of measurable disease. Therapy must be completed at least 4 weeks before the enrollment in study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Age > 18 years old.
• Adequate bone marrow reserve, indicated by absolute neutrophil count (ANC) ≥ 1000/mm³, platelets ≥50,000/mm³(25,000/mm³ if thrombocytopenia secondary to bone marrow involvement by lymphoma), and hemoglobin ≥8 g/dL. These values must be obtained within 2 weeks before protocol entry.
• Adequate liver function, indicated by bilirubin ≤1.5 times the upper limit of normal (ULN), alanine transaminase (ALT) ≤2 times the ULN or aspartate transaminase (AST) ≤2.0 times the ULN and albumin > 3.0 g/dl.
• Adequate renal function, indicated by serum creatinine ≤2.5 mg/dL. Laboratory values must be obtained within 2 weeks before study entry.
• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
• Able to give informed consent.

Exclusion Criteria:

• Patients with diagnosis of Mycosis Fungoides or Sezary Syndrome
• Patients with active Hepatitis B or Hepatitis C infection.
• Patients with known HIV infection are excluded. These patients are excluded because the potential to target activated T-cells, in a population of patients already at risk for T-cell depletion, would be a contraindication to therapy. HIV testing is not required.
• Patients with active infections requiring specific anti-infective therapy are not eligible until all signs of infections are resolved and any continuing treatment is given on an outpatient basis.
• Patients with previous anthracycline therapy (cumulative dose of > 100 mg/m2).
• Patients with Left Ventricular Ejection Fraction (LVEF) < 50%.
• Patients who are pregnant or breast-feeding. These patients are excluded because the effects of this treatment on the fetus and young children are unknown.
• Prior invasive malignancies within past 5 years.
• Allergic to or history of allergy to diphtheria toxin or IL-2.
• Preexisting severe cardiovascular disease (e.g. CHF, Severe CAD, cardiomyopathy, MI within past 3 months, arrhythmia) requiring ongoing treatment.
• Ongoing antineoplastic chemotherapy, radiation, hormonal (excluding contraceptives) or immunotherapy, or investigational medications within past 30 days.
• Patients with deep vein thrombosis within 3 months.