Belinostat Injection: Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Pralatrexate Injection: Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
CHOP: CHOP is the comparator arm
COP: COP is given in combination with Pralatrexate
Study summary
Part 1: This is a 5 Arm study primarily to determine the best dose out of the two dose levels of Belinostat and Pralatrexate combined with CHOP/COP in newly diagnosed PTCL patients based on Safety for part 2 study.
Part 2 (Efficacy and Safety): This is a 3 Arm study. Patients with previously untreated PTCL will be randomized 1:1:1 into 1 of 3 treatment groups: 2 experimental treatment groups (Bel-CHOP or Fol-COP) or 1 active comparator treatment group (CHOP). Patients will be treated for up to 6 cycles. The primary objective is to compare the Progression Free Survival of patients with newly diagnosed PTCL treated for up to 6 cycles with Beleodaq (belinostat) in combination with CHOP (Bel-CHOP) or Folotyn (pralatrexate injection) in combination with COP (Fol-COP) to CHOP alone.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 that it can be sent to the Sponsor (or designee) for later 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) patients are eligible only if Brentuximab Vedotin (BV) is not commercially approved for use, not available in the country or patient is contraindicated 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; and subcutaneous panniculitis-like T-cell lymphoma
2. CD30 expression and T-cell Follicular Helper (TFH) phenotype status must be available for documentation.
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 (ECOG) status ≤2
4. For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by:
1. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement
2. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of 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×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
5. 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 ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement
2. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of 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 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
5. Calculated creatinine clearance of ≥ 60 mL/min
6. UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal) and must be available for documentation.
7. 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
8. Patient (male or female) is at least 18 years of age at the time of informed consent
9. Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 6 months after the last dose of study treatment.
10. 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:
A patient will not be eligible for inclusion if ANY of the criteria listed below apply:
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 if they can be treated with Brentuximab Vedotin (BV)
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 (i.e. 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 status on the following:
1. Has a known HIV-positive diagnosis with uncontrolled and detectable viral load
2. Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and 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
Primary outcome measure(s)
PFS — 4.5 years Progression-free survival is determined from randomization to the first documented Progression of Disease or death, whichever occurs first.
Trial sites (69)
Facility
City
Region
Status
University of California, San Francisco Fresno
Clovis
California
Recruiting
University of California, Los Angeles Hem/ Onc Clinical Research Unit, Suite 600
Santa Monica
California
Recruiting
University of Colorado School of Medicine
Aurora
Colorado
Recruiting
Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System Memorial Cancer Institute
Pembroke Pines
Florida
Recruiting
Norton Cancer Institute
Louisville
Kentucky
Recruiting
Henry Ford Health System
Detroit
Michigan
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Recruiting
Valley Cancer Associates
Harlingen
Texas
Withdrawn
Houston Methodist Hospital
Houston
Texas
Withdrawn
University of Texas, MD Anderson Cancer Center
Houston
Texas
Recruiting
Baylor Scott & White Medical Center - Temple
Temple
Texas
Recruiting
The Ottawa Hospital
Ottawa
Ontario
Recruiting
Princess Margaret Hospital
Toronto
Ontario
Recruiting
Universitatsmedizin Gottingen
Göttingen
Germany
Recruiting
Universitaetsklinikum Halle (Saale)
Halle
Germany
Recruiting
University of Debrecen Clinical Center
Debrecen
Nagyerdei Krt. 98
Recruiting
Andras Josa University Teaching Hospital
Nyíregyháza
Szent Istvan Utca
Recruiting
Semmelweis Egyetem
Budapest
Hungary
Recruiting
National Institute of Oncology
Budapest
Hungary
Recruiting
Markhot Ferenc Oktato Korhaz
Eger
Hungary
Withdrawn
Belgyogyaszati Klinika es Kardiologiai Kozpont
Szeged
Hungary
Recruiting
Azienda Ospedaliera Cardinale Giovanni Panico
Tricase
Apulia
Recruiting
University of Milano Bicocca
Milan
Bicocca
Recruiting
Servizio Sanitario Regionale Emilia-Romagna-Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori" Srl (IRST)
Meldola
Province Of Forlì-Cesena
Recruiting
Policlinico GB Rossi Borgo Roma
Borgo Roma
Verona
Recruiting
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo
Alessandria
Italy
Recruiting
Ospedale Policlinico San Martino, IRCCS
Genova
Italy
Recruiting
Azienda Ospedaliera Universitaria di Parma
Parma
Italy
Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia
Italy
Recruiting
Azienda USL di Ravenna
Ravenna
Italy
Recruiting
University Hospital in Wroclaw
Wroclaw
Wroclaw
Recruiting
Pratia MCM Krakow
Krakow
Poland
Recruiting
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw
Poland
Recruiting
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz
Łódź Voivodeship
Recruiting
Inje University Busan Paik Hospital
Busan
Busanjin District
Recruiting
Ulsan University Hospital
Ulsan
Dong-gu
Withdrawn
Ajou University Hospital
Suwon
Gyenoggi-do
Recruiting
The Catholic University of Korea - St. Vincents Hospital
Suwon
Gyeonggi-do
Recruiting
Gyeongsang National University Hospital
Jinju
Gyeongsangnam-do
Withdrawn
Jeonbuk National University Hospital
Jeonju
Jeollabuk-do
Withdrawn
+ 29 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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