A Phase 3, Randomized, Open-Label Study Comparing the Efficacy and Safety of the Combination of Beleodaq-CHOP or Folotyn-COP to the CHOP Regimen Alone in Newly Diagnosed Patients with Peripheral T-Cell Lymphoma

Inclusion Criteria

1. 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:

1. 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

2. CD30 expression

3. TFH phenotype

2. 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)

3. Patient has an Eastern Cooperative Oncology Group performance status ≤2

4. 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

5. 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:

1. Absolute neutrophil count ≥1.0×109/L or >= ≥1.5×109/L if bone marrow involvement

2. Platelet count ≥100×109

- L or ≥75×109

- L if bone marrow involvement

3. Total bilirubin ≤1.5 mg/dL

4. 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)

5. Serum creatinine ≤2.0×ULN

6. Calculated creatinine clearance of ≥60 mL/min

6. UGT1A1 genotype has been characterized (see Belinostat dose modifications if

abnormal).

7. A decision whether to use prophylactic growth factor for cycle 1 or not has been made

8. 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

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

10. 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

11. 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

1. Patients with a diagnosis of:

1. Precursor T-cell lymphoma or leukemia

2. Adult T-cell lymphoma/leukemia

3. T-cell prolymphocytic leukemia

4. T-cell large granular lymphocytic leukemia

5. Primary cutaneous type ALCL

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

7. ALCL except if Brentuximab Vendotin cannot be utilized

2. 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

3. 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

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

5. 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

6. Patient with uncontrolled hypertension

7. 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

8. Patient with central nervous system metastasis

9. 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

10. 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

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

12. Pregnant or breastfeeding women