Intervention: Pralatrexate
Trial phase: Phase 3
ATC code: L01BA05
SMILES: C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 71
Group description: Vitamin B12 and folic acid will be taken concurrently with pralatrexate

pralatrexate: 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.

Vitamin B12 and folic acid: 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.
Eligibility criteria:
Inclusion Criteria:

Subject has histologically/cytologically confirmed PTCL, using the World Health Organization (WHO) disease classification:

PTCL not otherwise specified (NOS)
Angioimmunoblastic T-cell lymphoma
Anaplastic large cell lymphoma, ALK+
Anaplastic large cell lymphoma, ALK-
Extranodal NK/T-cell lymphoma - nasal type
Enteropathy-associated T cell lymphoma
Hepatosplenic T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
Aggressive NK-cell leukemia
Transformed mycosis fungoides
Subject has to have documented progressive disease (PD) after at least 1 prior systemic treatment.
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.
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.
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
At least 18 years of age.
Expected life expectancy ≥ 3 months.

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
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.
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.
Subject gives written informed consent (IC).

Exclusion Criteria:

Subject has:

Precursor T-cell lymphoma or leukemia
T-cell prolymphocytic leukemia (T-PLL)
T-cell large granular lymphocytic leukemia
Mycosis fungoides, other than transformed mycosis fungoides
Sézary syndrome
Primary cutaneous CD30+ T-cell disorders: Lymphoid papulosis and primary cutaneous anaplastic large cell lymphoma
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.
Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure guidelines.
Human immunodeficiency virus (HIV)-positive diagnosis.
Has, or history of, brain metastases or central nervous system (CNS) disease.
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.
Has 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 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.
Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
Receipt of anti-tumor antibody therapy within 100 days prior to study treatment.
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.
Previous exposure to pralatrexate.
Subject is pregnant or breast-feeding