Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients
Condition: Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Pralatrexate Injection
Intervention description: Intravenous (IV) push administration over 30 seconds to 5 minutes via a patent IV line containing normal saline (0.9% sodium chloride).
Initial dose: 30 mg/m2
Administered weekly for 3 weeks of a 4-week cycle until criteria for discontinuation per the protocol are met.
Intervention MeSH terms: 10-deazaaminopterin; Aminopterin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoproliferative Disorders; Lymphoma; Non-Hodgkin's Lymphoma; T-cell Lymphoma

Summary:

      The purpose of this study is to see if pralatrexate extends response and survival following
      CHOP-based chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone)
      and if pralatrexate improves response in patients with partial response following CHOP-based
      chemotherapy. Patients will either receive pralatrexate or be under observation. All patients
      will receive vitamins B12 and folic acid and attend regular clinic visits to evaluate their
      disease and health.
    

Eligibility criteria:

        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.