Study of Pralatrexate Versus Observation Following CHOP-based Chemotherapy in Previously Undiagnosed Peripheral T-cell Lymphoma Patients

Inclusion Criteria:

• Patient has one of the following peripheral T-cell lymphoma (PTCL) subtypes confirmed by an independent central pathology reviewer, using the Revised European American Lymphoma World Health Organization disease classification:

  • T/natural killer (NK)-cell leukemia/lymphoma
  • Adult T-cell lymphoma (TCL)/leukemia (human T-cell leukemia virus 1+)
  • Angioimmunoblastic TCL
  • Anaplastic large cell lymphoma (ALCL), primary systemic type, excluding anaplastic lymphoma kinase positive (ALK+) with International Prognostic Index (IPI) score less than 2 at initial diagnosis and complete response (CR) after CHOP-based therapy
  • PTCL-unspecified
  • Enteropathy-type intestinal lymphoma
  • Hepatosplenic TCL
  • Subcutaneous panniculitis TCL
  • Transformed mycosis fungoides (tMF)
  • Extranodal T/NK-cell lymphoma nasal or nasal type
  • Primary cutaneous gamma-delta TCL
  • Primary cutaneous CD8+ aggressive epidermic cytotoxic TCL

• Documented completion of at least 6 cycles of CHOP-based therapy:

  • CHOP 21
  • CHOP 14
  • CHOP + etoposide
  • Other CHOP variants: substitution allowed for 1 component with a drug of the same mechanism of action. Additional components, except alemtuzumab, are allowed. Rituximab may be added if not given within 3 cycles of randomization.
• Patient has achieved CR or partial response (PR) per per investigator's assessment following completion of CHOP-based therapy and has had radiological assessment within 21 days prior to randomization.
• Eastern Cooperative Oncology Group performance status less than or equal to 2.
• Adequate blood, liver, and kidney function as defined by laboratory tests.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate.
• Men who are sexually active, including those with a pregnant partner, must agree to practice a medically acceptable barrier method contraceptive regimen (eg, condoms) while receiving pralatrexate and for 90 days after the last administration of pralatrexate.
• Has given written informed consent.

Exclusion Criteria:

• Patient has:

  • Precursor T/NK neoplasms
  • ALCL (ALK+) with IPI score less than 2 at initial diagnosis and CR after CHOP-based therapy
  • T cell prolymphocytic leukemia
  • T cell large granular lymphocytic leukemia
  • Mycosis fungoides, except tMF
  • Sézary syndrome
  • Primary cutaneous CD30+ disorders: ALCL and lymphomatoid papulosis

• If there is a history of prior malignancies other than those below, must be disease free for at least 5 years. Patients with malignancies listed below less than 5 years before study entry may be enrolled if they have received treatment resulting in complete resolution of the cancer and have no clinical, radiologic, or laboratory evidence of active/recurrent disease.

  • non-melanoma skin cancer
  • carcinoma in situ of the cervix
  • localized prostate cancer
  • localized thyroid cancer

• Receipt of prior chemotherapy (CT) or radiation therapy (RT) for PTCL, other than a single allowed CHOP regimen, except:

  • Patients with nasal NK lymphoma who received local RT less than 4 weeks prior to randomization.
  • Patients with tMF who received 1 systemic single-agent CT (except methotrexate) prior to transformation.
• Prior exposure to pralatrexate.
• Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of 10 mg/day or less of oral prednisone or equivalent for at least 4 weeks or as part of a CHOP prednisone taper.
• Planned use of any treatment for PTCL during the course of the study.

• Patient has:

  • Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of less than 100 mm3 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
  • Hepatitis B (HBV)-positive serology and is receiving interferon therapy or has liver function test results outside the parameters of study inclusion criteria. Other antiviral therapies are permitted if at a stable dose for at least 4 weeks.
  • Hepatitis C (HCV) virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
  • Symptomatic central nervous system metastases or lesions requiring treatment.
  • Uncontrolled hypertension or congestive heart failure Class III/IV per the New York Heart Association's Heart Failure Guidelines
  • Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness impairing the ability of the patient to receive protocol treatment.
• Major surgery within 2 weeks prior to study entry, except for line placement or biopsy procedure.