A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL
Condition: Refractory Peripheral T-Cell Lymphoma; Relapsed T-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: pralatrexate; Vitamin B12 and folic acid
Intervention description: Pralatrexate will be administered at a dose of 30 mg/m2/week for 6 weeks followed by 1 week of rest in a 7-week cycle. Pralatrexate administration occurs once a week during week 1 through week 6 of each cycle.; The eligible subjects will receive vitamin supplementation at screening phase, at least 10 days prior to pralatrexate administration on cycle 1, dose 1. Vitamin supplementation will consist of vitamin B12 1 mg intramuscular (IM) q 8-10 weeks and folic acid 1.2mg by mouth (PO) once a day (QD). Once pralatrexate is permanently discontinued, vitamin supplementation should continue at least 1 month after the last pralatrexate dose, or longer at the discretion of the investigator.
Intervention MeSH terms: Folic Acid; Vitamin B 12; Hydroxocobalamin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: FOT12-CN-301; PTCL (peripheral T-cell lymphoma); pralatrexate; vitamin B12; folic acid

Summary:

      This is a single arm, open-label, multi-center study designed to demonstrate the efficacy and
      safety of pralatrexate when administered concurrently with vitamin B12 and folic acid
      supplementation to patients with relapsed or refractory peripheral T-cell lymphoma(PTCL).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject has histologically/cytologically confirmed PTCL, using the World Health
             Organization (WHO) disease classification:

               1. PTCL not otherwise specified (NOS)

               2. Angioimmunoblastic T-cell lymphoma

               3. Anaplastic large cell lymphoma, ALK+

               4. Anaplastic large cell lymphoma, ALK-

               5. Extranodal NK/T-cell lymphoma - nasal type

               6. Enteropathy-associated T cell lymphoma

               7. Hepatosplenic T-cell lymphoma

               8. Subcutaneous panniculitis-like T-cell lymphoma

               9. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)

              10. Aggressive NK-cell leukemia

              11. Transformed mycosis fungoides

          2. Subject has to have documented progressive disease (PD) after at least 1 prior
             systemic treatment.

          3. Subject may not have received an experimental drug or biologic as their only prior
             therapy. Subject must have clear PD after the last treatment received. Subject should
             have at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm
             the diagnosis of PTCL. Subject must have recovered from the toxic effects of prior
             therapy.

          4. Subjects with an enlarged lymph node or extranodal mass lesion clearly measurable in
             two perpendicular directions and greater than 1.5 cm maximum diameter on computed
             tomography performed within 14 days prior to study enrollment.

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

          6. At least 18 years of age.

          7. Expected life expectancy ≥ 3 months.

          8. Adequate hematological, hepatic, and renal function as defined by:

               -  Absolute neutrophil count (ANC) ≥ 1000/uL (or 1*109/L), platelet count ≥
                  100,000/uL (or 100*109/L) (at both screening and within 3 days prior to dosing on
                  cycle 1, day 1)

               -  Total bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine
                  aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN) (AST/ALT < 5 X ULN if
                  documented hepatic involvement with lymphoma)

               -  Creatinine ≤ 1.5 mg/dL (or 132.6 µmol/L) or a calculated creatinine clearance ≥
                  50 mL/min

          9. Women of childbearing potential must have agreed 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. Subjects who are
             postmenopausal for at least 1 year (> 12 months since last menses) or are surgically
             sterilized did not require this test.

         10. 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.

         11. Subject gives written informed consent (IC).

        Exclusion Criteria:

          1. Subject has:

               1. Precursor T-cell lymphoma or leukemia

               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+ T-cell disorders: Lymphoid papulosis and primary
                  cutaneous anaplastic large cell lymphoma

          2. 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.

          3. Congestive heart failure Class III/IV according to the New York Heart Association's
             Heart Failure guidelines.

          4. Human immunodeficiency virus (HIV)-positive diagnosis.

          5. Has, or history of, brain metastases or central nervous system (CNS) disease.

          6. Active uncontrolled infection, underlying medical condition including unstable cardiac
             disease, or other serious illness that would impair the ability of the subject to
             receive protocol treatment.

          7. Has major surgery within 2 weeks of study entry.

          8. 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.

          9. Receipt of corticosteroids within 7 days of study treatment, unless subject has been
             taking a continuous systemic dose of no more than 10 mg/day or equivalent dose of
             prednisone, or a local or inhaled or intranasal administration at fixed doses for at
             least 1 month prior to study treatment and tumor shrinkage was not observed.

         10. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study
             treatment or planned use during the course of the study.

         11. Receipt of anti-tumor antibody therapy within 100 days prior to study treatment.

         12. History of allogeneic hematopoietic stem cell transplantation. Or subjects with a
             history of autologous hematopoietic stem cell transplantation within 100 days prior to
             study treatment.

         13. Previous exposure to pralatrexate.

         14. Subject is pregnant or breast-feeding