Inclusion Criteria:

• Confirmed relapsed or refractory cutaneous T-cell lymphoma (CTCL):

  1. Mycosis fungoides Stage IB or higher
  2. Sézary syndrome
  3. Primary cutaneous anaplastic large cell
• No curative treatment options.
• Progression of disease (PD) or relapse of disease after at least 1 previous systemic therapy, PD after last prior treatment regimen, and recovered from the toxic effects of prior therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Life expectancy ≥ 3 months.
• Adequate blood, liver, and kidney function as determined by laboratory tests.
• Methylmalonic acide (MMA) serum concentration < 200 nmol/L and homocysteine (Hcy) concentration < 10 μmol/L at screening, or receipt of 1 mg daily oral folic acid for at least 10 days prior to the planned start of pralatrexate and 1 mg intramuscular vitamin B12 within 10 weeks of the planned start of pralatrexate.
• Women of childbearing potential must use a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last dose of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Serum pregnancy test not required for patients who are postmenopausal (greater than 12 months since last menses) or are surgically sterilized.
• Women who are breastfeeding.
• Men who are not surgically sterile must use a medically acceptable contraceptive regimen from start of pralatrexate until at least 90 days after the last administration of pralatrexate.
• Written informed consent and privacy authorization.

Exclusion Criteria:

• Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 5 years. Patients with other prior malignancies < 5 years before study entry may be enrolled if treatment resulted in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease.
• Congestive heart failure Class III/IV per the New York Heart Association Heart Failure Guidelines.
• Uncontrolled hypertension.
• Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of <100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy.
• Symptomatic central nervous system metastases or lesions for which treatment is required.
• Active uncontrolled infection, underlying medical condition that would impair ability to receive protocol treatment.
• Major surgery within 2 weeks of planned start of treatment.
• Receipt of any conventional chemotherapy or radiation therapy (RT) encompassing >10% of bone marrow within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the study.
• Receipt of systemic corticosteroids within 3 weeks of study treatment, unless on a continuous dose of ≤10 mg/day of prednisone for at least 1 month.
• Initiation of or change in dosage of topical corticosteroids within 3 weeks of study treatment (topical steroid use within 3 weeks is allowed if strength/use has been stable for at least 1 month; topical corticosteroids cannot be started during the study).
• Use of investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the study.
• Receipt of a monoclonal antibody within 3 months without evidence of progression.
• Use of oral retinoids within 4 weeks of study treatment or high-dose vitamin A.
• Previous exposure to pralatrexate, unless the patient was on this study, achieved a complete or partial response, and was taken off study treatment because of investigator decision, and subsequently experienced disease recurrence or progressive disease.
• Re-entering patients: must not have received subsequent therapy for CTCL during the time off initial study treatment.