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

Inclusion Criteria:

1. Patient with newly diagnosed, untreated histology-proven PTCL based on localpathology review who is eligible for receiving, Belinostat, Pralatrexate, and CHOP.Pathology material must be available at the site for each patient before enrollmentso that it can be sent to the Sponsor (or designee) for later confirmation. Thefollowing subtypes, as defined by the updated World Health Organization (WHO)classification, may be included. This information should be available foreligibility:

2. Pathology subtype:

• Peripheral T-cell lymphoma, not otherwise specified
• Angioimmunoblastic T-cell lymphoma
• Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) patients are eligible only if Brentuximab Vedotin (BV) is notcommercially approved for use, not available in the country or patient iscontraindicated to receive BV.
• Follicular T-cell lymphoma
• Others: Extra-nodal natural killer/T-cell lymphoma, nasal type;enteropathy-associated T-cell lymphoma; hepatosplenic T-cell lymphoma; andsubcutaneous panniculitis-like T-cell lymphoma

2. CD30 expression and T-cell Follicular Helper (TFH) phenotype status must beavailable for documentation.

3. Patient has at least 1 site of measurable disease according to Response EvaluationCriteria in Lymphoma (RECIL) 2017 criteria as assessed by the local Investigator (Appendix 3)

4. Patient has an Eastern Cooperative Oncology Group performance (ECOG) status ≤2

5. For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renalfunction as defined by:

6. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bonemarrow involvement

7. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement

8. Total bilirubin ≤1.5 mg/dL

9. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepaticinvolvement with lymphoma)

10. Calculated creatinine clearance of ≥ 60 mL/min

11. Part 2 (Efficacy and Safety) - disease related hypoplasia, hepatological or renaldysfunction can be included if any of the treatment groups can be administered basedon package insert recommendation with the following restrictions:

12. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bonemarrow involvement

13. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement

14. Total bilirubin ≤1.5 mg/dL

15. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documentedhepatic involvement with lymphoma)

16. Calculated creatinine clearance of ≥ 60 mL/min

17. UGT1A1 genotype has been characterized (see Belinostat dose modifications ifabnormal) and must be available for documentation.

18. Patient must be willing and capable of giving written informed consent and must beable to adhere to dosing and visit schedules and meet all study requirements

19. Patient (male or female) is at least 18 years of age at the time of informed consent

20. Patient is willing to practice 2 forms of contraception, one of which must be abarrier method, from study entry until at least 6 months after the last dose ofstudy treatment.

21. Females of childbearing potential must have a negative urine pregnancy test within 4weeks prior to the first day of study treatment. Females who are postmenopausal forat least 1 year (defined as more than 12 months since last menses) or are surgicallysterilized do not require this test.

Exclusion Criteria:

A patient will not be eligible for inclusion if ANY of the criteria listed below apply:

1. Patients with a diagnosis of:

2. Precursor T-cell lymphoma or leukemia

3. Adult T-cell lymphoma/leukemia

4. T-cell prolymphocytic leukemia

5. T-cell large granular lymphocytic leukemia

6. Primary cutaneous type ALCL

7. Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome)

8. ALCL if they can be treated with Brentuximab Vedotin (BV)

9. Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one weekbefore randomization; drug can be resumed if the treatment doesn't includebelinostat

10. Patient with an active concurrent malignancy/life-threatening disease with theexception of non melanoma skin tumors and in situ cervical cancer if they havereceived treatment resulting in complete resolution of the cancer and currently haveno clinical, radiologic, or laboratory evidence of active or recurrent disease. Ifthere is a history of prior malignancies/life-threatening diseases, the patient mustbe disease free for at least 5 years

11. Prior histone deacetylase (HDAC) inhibitor or pralatrexate therapy

12. Any known cardiac abnormalities such as baseline prolongation of QT/corrected QT (QTc) interval (i.e. demonstration of a QTc interval >450 msec); long QT syndrome;myocardial infarction within 6 months prior to starting study; history ofsignificant cardiovascular disease; the required use of a concomitant medicationthat may cause Torsades de Pointes

13. Patient with uncontrolled hypertension

14. Patients status on the following:

15. Has a known HIV-positive diagnosis with uncontrolled and detectable viral load

16. Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and detectableviral load or immunological evidence of chronic active disease

17. Patient with central nervous system metastasis

18. Patient with an active uncontrolled infection, underlying medical condition,laboratory abnormality, or other serious illness that would impair the ability ofthe patient to receive protocol treatment

19. Patient who has used any investigational drugs, biologics, or devices within 28 daysprior to study treatment or plans to use any of these during the course of the study

20. Patient with a known history of drug or alcohol abuse

21. Pregnant or breastfeeding women