Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
Condition: Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Pralatrexate Injection
Intervention description: Pralatrexate 30 mg/m2 via IV push over 3-5 minutes for 6 weeks in a 7 week cycle.
Intervention MeSH terms: 10-deazaaminopterin; Aminopterin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Peripheral T-cell Lymphoma; T-cell Lymphoma; Lymphoma; PDX; Pralatrexate; Vitamin B12; Folic acid

Summary:

      Primary

      • Determine the efficacy of pralatrexate with concurrent vitamin B12 and folic acid
      supplementation when administered to patients with relapsed or refractory peripheral T-cell
      lymphoma (PTCL)

      Secondary

        -  Determine the safety of pralatrexate with concurrent vitamin B12 and folic acid
           supplementation when administered to patients with relapsed or refractory PTCL

        -  Determine the pharmacokinetic (PK) profile of pralatrexate when administered with
           vitamin B12 and folic acid supplementation
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically confirmed PTCL, using the Revised European American
             Lymphoma (REAL) World Health Organization (WHO) disease classification:

               1. T/Natural Killer (T/NK) cell leukemia/lymphoma

               2. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)

               3. Angioimmunoblastic T cell lymphoma

               4. Blastic Natural Killer (NK) lymphoma (with skin, lymph node, or visceral
                  involvement)

               5. Anaplastic large cell lymphoma, primary systemic type

               6. PTCL - unspecified

               7. T/NK-cell lymphoma - nasal

               8. Enteropathy-type intestinal lymphoma

               9. Hepatosplenic T cell lymphoma

              10. Extranodal peripheral T/NK-cell lymphoma - unspecified

              11. Subcutaneous panniculitis T-cell lymphoma

              12. Transformed mycosis fungoides

          -  Documented progression of disease after at least 1 prior treatment. Patients may not
             have received experimental therapy as their only prior therapy. Patient has at least 1
             biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of
             PTCL. Patient has recovered from the toxic effects of prior therapy. Patients treated
             with monoclonal antibody therapy may be enrolled regardless of the time frame of the
             therapy if they have progression of disease.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

          -  ≥ 18 years of age.

          -  Adequate hematological, hepatic, and renal function.

          -  Women of childbearing potential must agree to practice a medically acceptable
             contraceptive regimen from study treatment initiation until at least 30 days after the
             last administration of pralatrexate and must have a negative serum pregnancy test
             within 14 days prior to the first day of study treatment. Patients who are
             postmenopausal for at least 1 year or are surgically sterilized do not require this
             test.

          -  Men who are not surgically sterile must agree to practice a medically acceptable
             contraceptive regimen from study treatment initiation until at least 90 days after the
             last administration of pralatrexate.

          -  Patient has given written informed consent.

        Exclusion Criteria:

          -  Patient has:

               1. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma

               2. T cell prolymphocytic leukemia (T-PLL)

               3. T cell large granular lymphocytic leukemia

               4. Mycosis fungoides, other than transformed mycosis fungoides

               5. Sézary syndrome

               6. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and
                  lymphomatoid papulosis

          -  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 greater than or equal to 5 years.

          -  Congestive heart failure Class III/IV according to the New York Heart Association's
             Heart Failure Guidelines.

          -  Uncontrolled hypertension.

          -  Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination
             anti-retroviral therapy.

          -  Patient has, or history of, brain metastases or central nervous system (CNS) disease.

          -  Patient has undergone an allogeneic stem cell transplant.

          -  Patient has relapsed less than 75 days from time of an autologous stem cell
             transplant.

          -  Active uncontrolled infection, underlying medical condition including unstable cardiac
             disease, or other serious illness that would impair the ability of the patient to
             receive protocol treatment.

          -  Major surgery within 2 weeks of study entry.

          -  Receipt of any conventional chemotherapy or radiation therapy (RT) within 4 weeks (6
             weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during
             the course of the study.

          -  Receipt of corticosteroids within 7 days of study treatment, unless patient has been
             taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.

          -  Use of any investigational drugs, biologics, or devices within 4 weeks prior to study
             treatment or planned use during the course of the study.

          -  Previous exposure to pralatrexate.