Peripheral T-cell Lymphoma

Primary objective: • To evaluate the objective response rate to pralatrexate in Asian PTCL patients after prior treatment failure, as determined by independent imaging reviewer(s) using international workshop lymphoma response criteria (IWC) Secondary objectives: • To determine the safety of pralatrexate in Asian PTCL patients by, - Incidence of adverse events (AEs) and serious adverse events (SAEs) emergent from the treatment • To evaluate the efficacy of pralatrexate in Asian PTCL patients after prior treatment failure by, - Overall survival (OS), progression-free-survival (PFS), complete response (CR) and partial response (PR) rate, and duration of CR and PR - Treatment duration with pralatrexate in the patients without hematopoietic stem cell transplant (HSCT) who achieve CR or PR - Percentage of patients who undergo HSCT - 1-year OS, 1-year PFS, and 1-year relapse rate after HSCT - 2-year OS, 2-year PFS, and 2-year relapse rate after HSCT

FOLOTYN Solution for intravenous injection

pralatrexate

injection

1.00mg

1. Primary endpoint:
(1). Objective response rate (ORR) to pralatrexate treatment in Asian PTCL patients after prior treatment failure, as determined by independent imaging reviewer(s) using international lymphoma response criteria
2. Secondary endpoints:
(1). Incidence of treatment emergent adverse events (AE) and serious adverse events (SAE)
(2). OS, PFS, CR and PR rate, Duration of CR and PR
(3). Treatment duration with pralatrexate in the patients without HSCT who achieve CR or PR
(4). Percentage of patients who undergo HSCT
(5). 1-year OS, 1-year PFS, and 1-year relapse rate after HSCT
(6). 2-year OS, 2-year PFS, and 2-year relapse rate after HSCT
** HSCT includes autologous and allogeneic stem cell transplantation.

1. Main inclusion criteria (patients who meet all inclusion criteria will be included):
(1). At least 20 years of age, inclusive
(2). Patients with histologically/cytologically confirmed PTCL using either: NCCN diagnosis criteria, the Revised European American Lymphoma (REAL), and World Health Organization (WHO) disease classification (PTCL diagnosed by site investigators, PTCL histology/cytology subtypes confirmed by study central pathology lab):
a. Peripheral T-cell lymphoma, NOS
b. Angioimmunoblastic T-cell lymphoma
c. Enteropathy-type T-cell lymphoma
d. Hepatosplenic T-cell lymphoma
e. Extranodal NK/T-cell lymphoma, nasal type
f. Subcutaneous panniculitis-like T-cell lymphoma
g. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
(3). Patients with documented progressive disease (PD) after 1 prior treatment
a. Patients may not have received an experimental drug or biologic as their only prior therapy
b. Patient has had at least 1 biopsy from initial diagnosis of PTCL, and preferably should have 1 biopsy in the relapsed setting to confirm current progression is due to PTCL
c. Patient has recovered from the toxic effects of prior therapy
(4). Eastern Cooperative Oncology Group (ECOG) Performance Status < 2.
(5). Adequate hematological, hepatic, and renal function as defined by: absolute neutrophil count (ANC) ≥ 1000/µL, platelet count ≥ 50,000/µL, 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 a calculated creatinine clearance ≥ 50 mL/min.
(6). Women of childbearing potential must agree to practice medically acceptable contraceptive regimen from 30 days prior to study treatment initiation until at least 30 days after the last administration of pralatrexate and must have had 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 (> 12 months since last menses) or were surgically sterilized do not require this test.
(7). 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.
(8). Patient has provided written informed consent (IC)

2. Main exclusion criteria (patients who meet any exclusion criteria will be excluded):
(1). Patient has following subtypes (histologically/cytologically confirmed) of PTCL
a) Anaplastic large cell lymphoma, ALK +/-
b) Patient has: Precursor T/NK neoplasms, with the exception of blastic NK lymphoma
c) T-cell prolymphocytic leukemia (T-PLL)
d) T-cell large granular lymphocytic leukemia
e) Mycosis fungoides and transformed mycosis fungoides
f) Sézary syndrome
g) Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis
(2). Active concurrent malignancy (except for 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). Patients with human immunodeficiency virus (HIV)-positive diagnosis and are receiving combination anti-retroviral therapy.
(5). Current or the history of brain metastases or central nervous system (CNS) diseases
(6). Have undergone allogeneic stem cell transplant
(7). Relapsed less than 75 days from time of autologous stem cell transplant
(8). Patients with uncontrolled hypertension, 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
(9). Had major surgery within 2 weeks of study entry
(10). 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
(11). Receipt of corticosteroids within 7 days of study treatment, unless patient has been taking a stable dose of no more than 10 mg/day of prednisone for at least 1 month
(12). Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study
(13). Previous exposure to pralatrexate
(14). Other conditions that investigators consider not suitable for study enrollment