To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL (CRESCENDO)

Inclusion Criteria: Patient with newly diagnosed, untreated histology-proven PTCL based on local pathology review who is eligible for receiving, Belinostat, Pralatrexate, and CHOP. Pathology material must be available at the site for each patient before enrollment so it can be sent to the Sponsor (or designee) for confirmation. The following subtypes, as defined by the updated World Health Organization (WHO) classification, may be included. This information should be available for eligibility: Pathology subtype: Peripheral T-cell lymphoma, not otherwise specified Angioimmunoblastic T-cell lymphoma Anaplastic lymphoma kinase (ALK)- negative anaplastic large-cell lymphoma (ALCL) Follicular T cell lymphoma Others: Extra-nodal natural killer/T-cell lymphoma, nasal type; enteropathy-associated T-cell lymphoma; hepatosplenic T-cell lymphoma; and subcutaneous panniculitis-like T-cell lymphoma CD30 expression TFH phenotype Patient has at least 1 site of measurable disease according to Response Evaluation Criteria in Lymphoma (RECIL) 2017 criteria as assessed by the local Investigator (Appendix 3) Patient has an Eastern Cooperative Oncology Group performance status ≤2 For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by: a. Absolute neutrophil count ≥1.5×109 L b. Platelet count ≥100×109 L c. Total bilirubin ≤1.5 mg/dL d. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤3×the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) e. Serum creatinine ≤2.0×ULN or calculated creatinine clearance of ≥60 mL/min Part 2 (Efficacy and Safety) - disease related hypoplasia, hepatological or renal dysfunction can be included if any of the treatment groups can be administered based on package insert recommendation with the following restrictions: Absolute neutrophil count ≥1.0×109/L or >= ≥1.5×109/L if bone marrow involvement Platelet count ≥100×109 L or ≥75×109 L if bone marrow involvement Total bilirubin ≤1.5 mg/dL Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤3×the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) Serum creatinine ≤2.0×ULN Calculated creatinine clearance of ≥60 mL/min UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal). A decision whether to use prophylactic growth factor for cycle 1 or not has been made Patient must be willing and capable of giving written informed consent and must be able to adhere to dosing and visit schedules and meet all study requirements Patient (male/female) is at least 18 years of age at the time of informed consent Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 30 days after the last dose of study treatment Females of childbearing potential must have a negative urine pregnancy test within 4 weeks prior to the first day of study treatment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test Exclusion Criteria: Patients with a diagnosis of: Precursor T-cell lymphoma or leukemia Adult T-cell lymphoma/leukemia T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Primary cutaneous type ALCL Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) ALCL except if Brentuximab Vendotin cannot be utilized Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week before randomization; drug can be resumed if the treatment doesn't include belinostat Patient with an active concurrent malignancy/life-threatening disease with the exception of non melanoma skin tumors and in situ cervical cancer if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. If there is a history of prior malignancies/life-threatening diseases, the patient must be disease free for at least 5 years Prior histone deacetylase (HDAC) inhibitor or pralatrexate therapy Any known cardiac abnormalities such as baseline prolongation of QT/corrected QT (QTc) interval (ie,demonstration of a QTc interval >450 msec); long QT syndrome; myocardial infarction within 6 months prior to starting study; history of significant cardiovascular disease; the required use of a concomitant medication that may cause Torsades de Pointes Patient with uncontrolled hypertension Patients with a known HIV-positive diagnosis, hepatitis B virus or hepatitis C virus diagnosis with detectable viral load or immunological evidence of chronic active disease Patient with central nervous system metastasis Patient with an active uncontrolled infection, underlying medical condition, laboratory abnormality, or other serious illness that would impair the ability of the patient to receive protocol treatment Patient who has used any investigational drugs, biologics, or devices within 28 days prior to study treatment or plans to use any of these during the course of the study Patient with a known history of drug or alcohol abuse Pregnant or breastfeeding women