To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
Start Date
10/4/2023
Completion Date
11/1/2030
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.
Detailed Description
Study Design and Treatment Plan: Part 1: Dose Finding It is a randomized, open label, multicenter study in patients with PTCL who have not been previously treated and the control arm is CHOP, COP, is the CHOP regimen without Doxorubicin (H). Two investigational agents are separately added to C(H)OP, Belinostat for Bel-CHOP and Pralatrexate for FOL-COP. In this first part, each investigational arm will have two dose levels which will be compared with CHOP as reference. Treatment will be randomized in five arms: 1. Group 1a (Bel-CHOP) Belinostat 600 mg/m2 2. Group 1b (Bel-CHOP) Belinostat 1000 mg/m2 3. Group 2a (Fol-COP) Pralatrexate 20 mg/m2 4. Group 2b (Fol-COP) Pralatrexate 30 mg/m2 5. Group 3 for CHOP alone. Analysis will be done when 75 patients have received their planned treatment cycles to evaluate treatment compliance. Approximately 20 patients will be enrolled into each group and receive at least one cycle of drug thus 15 patients are expected to be evaluated with their planned treatment of 6 cycles completed. The safety data will be evaluated to select the proper dose for Belinostat -CHOP and Pralatrexate-COP for the Part 2 study. Part 2: Efficacy and Safety It is a randomized, open-label, multicenter study in newly diagnosed PTCL patients. This is a three arm study and 143 patients will enroll in each arm. Patients will be randomized in a balance manner (1:1:1) into 1 of 3 treatment groups and treated for up to 6 cycles: Group 1: (Bel-CHOP): Belinostat at the dose determined from Part 1 (600 or 1000 mg/m2) to be administered on Day 1 by 30 min intravenous (IV) infusion once daily for 5 days; CHOP will also be administered starting on Day 1 within 15 min (±5 min) after the end of the belinostat infusion at the doses shown below for Group 3, with cycles repeated every 21 days for up to 6 cycles Group 2: (Fol-COP): Pralatrexate at the dose determined from part 1 (20 or 30 mg/m2) is to be administered on Day 1 and Day 8 as an IV push over 3 to 5 min; CHOP will also be administered starting on Day 1 within 15 min (±5 min) after the end of the pralatrexate administration at the doses shown below for Group 3, with cycles repeated every 21 days for up to 6 cycles. COP combination refers to CHOP without Doxorubicin (H). Group 3: (CHOP): Combination chemotherapy to be administered starting on Day 1 at the doses shown below, with cycles repeated every 21 days for up to 6 cycles * Cyclophosphamide 750 mg/m2 IV, Day 1 * Doxorubicin 50 mg/m2 IV, Day 1 (limit lifetime cumulative dose to \<550 mg/m² to reduce risk of cardiotoxicity) * Vincristine 1.4 mg/m2 (maximum 2 mg) IV, Day 1 * Prednisone 100 mg orally (PO) daily, Day 1 (after the end of the belinostat or pralatrexate administration for Groups 1 and 2) to Day 5 Randomization will be stratified on: * Histology (nodal, extra-nodal) * Prognostic Index for T-Cell Lymphoma (Group 1 or 2 vs 3 or 4) * Region (US, ex-US) The study duration will include up to a 28-day screening period, a 6-cycle treatment period (18 weeks), follow-up until progression, an End-of-Treatment Visit at least 30 days after the last dose of study treatment, and long-term survival follow-up for patients by phone every 6 months thereafter until a 5-year median follow-up of the population is reached. Patients discontinuing the study for other reasons than progression will have the same long-term follow-up for OS analysis. Tumor assessments will be performed every 3 cycles (i.e., 9 weeks) on Cycle 4 Day 1 and End-of-Treatment Visit during treatment, then every 3 months for 3 years for patients with complete response (CR), partial response (PR), or stable disease, and every 6 months thereafter until disease progression or death
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Belinostat Injection
Pralatrexate Injection
CHOP
COP
Conditions
Locations
University of California, San Francisco Fresno
Clovis, California 93611
United States
University of California, Los Angeles Hem/ Onc Clinical Research Unit, Suite 600
Santa Monica, California 90404
United States
University of Colorado School of Medicine
Aurora, Colorado 80045
United States
Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System Memorial Cancer Institute
Pembroke Pines, Florida 33026
United States
Norton Cancer Institute
Louisville, Kentucky 40207
United States
Henry Ford Health System
Detroit, Michigan 48202
United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey 08901
United States
Valley Cancer Associates
Harlingen, Texas 78550
United States
Houston Methodist Hospital
Houston, Texas 77030
United States
University of Texas, MD Anderson Cancer Center
Houston, Texas 77030
United States
Baylor Scott & White Medical Center - Temple
Temple, Texas 76508
United States
The Ottawa Hospital
Ottawa, Ontario K1H 8L6
Canada
Princess Margaret Hospital
Toronto, Ontario M5G 2C4
Canada
Universitatsmedizin Gottingen
Göttingen, 37075
Germany
Universitaetsklinikum Halle (Saale)
Halle, 06120
Germany
University of Debrecen Clinical Center
Debrecen, Nagyerdei Krt. 98 4032
Hungary
Andras Josa University Teaching Hospital
Nyíregyháza, Szent Istvan Utca 68
Hungary
Semmelweis Egyetem
Budapest, 1088
Hungary
National Institute of Oncology
Budapest, 1122
Hungary
Markhot Ferenc Oktato Korhaz
Eger, 3300
Hungary
Belgyogyaszati Klinika es Kardiologiai Kozpont
Szeged, 6725
Hungary
Azienda Ospedaliera Cardinale Giovanni Panico
Tricase, Apulia 73039
Italy
University of Milano Bicocca
Milan, Bicocca 20126
Italy
Servizio Sanitario Regionale Emilia-Romagna-Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori" Srl (IRST)
Meldola, Province Of Forlì-Cesena 47014
Italy
Policlinico GB Rossi Borgo Roma
Borgo Roma, Verona 37134
Italy
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo
Alessandria,
Italy
Ospedale Policlinico San Martino, IRCCS
Genova, 16132
Italy
Azienda Ospedaliera Universitaria di Parma
Parma, 43126
Italy
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Italy
Azienda USL di Ravenna
Ravenna, 41800
Italy
University Hospital in Wroclaw
Wroclaw, Wroclaw 50-367
Poland
Pratia MCM Krakow
Krakow, 30-727
Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw,
Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, Łódź Voivodeship 93-513
Poland
Inje University Busan Paik Hospital
Busan, Busanjin District
South Korea
Ulsan University Hospital
Ulsan, Dong-gu
South Korea
Ajou University Hospital
Suwon, Gyenoggi-do 16499
South Korea
The Catholic University of Korea - St. Vincents Hospital
Suwon, Gyeonggi-do
South Korea
Gyeongsang National University Hospital
Jinju, Gyeongsangnam-do
South Korea
Jeonbuk National University Hospital
Jeonju, Jeollabuk-do
South Korea
Yeungnam University Medical Center
Daegu, Nam-gu
South Korea
Severance hospital, Yonsei University
Sinchon-dong, Seoul
South Korea
Asan Medical Center
Songpa-dong, Seoul 05505
South Korea
Daegu Catholic University Medical Center
Daegu, 42472
South Korea
Gachon University Gil Medical Center
Incheon, 21565
South Korea
Samsung Medical Center
Seoul, 6351
South Korea
Seoul National University Hospital
Seoul,
South Korea
Hospital Universitario Basurto
Bilbao, Bizkaia 48013
Spain
Hospital Universitario Fundación Jiménez Díaz
Moncloa-Aravaca, Madrid 28040
Spain
Hospital Universitario de Navarra
Pamplona, Navarre 31008
Spain
Hospital del Mar Medical Research Institute
Barcelona, 08003
Spain
ICO - Hospital Duran i Reynals
Barcelona, 08908
Spain
Clinica Universidad de Navarra - Madrid
Madrid, 28027
Spain
Clinica Universidad de Navarra
Pamplona, 31008
Spain
Hospital Universitario de Salamanca
Salamanca, 37007
Spain
Hospital Universitario y Politecnico La Fe
Valencia, 46026
Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009
Spain
Changhua Christian Hospital CCH
Changhua, Changhua County
Taiwan
Hualien Tzu Chi Medical Center
Hualien City, Hualien 970
Taiwan
National Cheng Kung University Hospital NCKUH
Tainan, Southern Taiwan 704
Taiwan
Chang Bing Show Chwan Memorial Hospital
Changhua, 505
Taiwan
Hematology Oncology Taipei Medical University - Shuang-Ho Hospital
New Taipei City,
Taiwan
Chang Gung Memorial Hospital Linkou Branch
Taoyuan, 333
Taiwan
Ankara University Medical Faculty Hospital
Altındağ, Ankara 06230
Turkey (Türkiye)
Bilkent University
Çankaya, Ankara 06800
Turkey (Türkiye)
Gazi University Faculty of Medicine
Yenimahalle, Ankara 06560
Turkey (Türkiye)
VKV AMERICAN HOSPITAL, Medical Oncology Outpatient Clinic
Şişli, Istanbul 34365
Turkey (Türkiye)
Adana City Education and Research Hospital
Adana, 4522
Turkey (Türkiye)
Ege Univ. Hospital
Bornova, 35100
Turkey (Türkiye)