To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
CRESCENDO
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
2 other identifiers
interventional
504
10 countries
69
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Oct 2023
Longer than P75 for phase_3
69 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 19, 2023
CompletedStudy Start
First participant enrolled
October 4, 2023
CompletedFirst Posted
Study publicly available on registry
October 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2030
October 23, 2025
October 1, 2025
6.7 years
September 19, 2023
October 22, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
PFS
Progression-free survival is determined from randomization to the first documented Progression of Disease or death, whichever occurs first.
4.5 years
Secondary Outcomes (1)
Overall survival
8 years
Study Arms (5)
Group 1a
ACTIVE COMPARATORGroup 1a Belinostat 600 mg/m2 + CHOP
Group 1b
ACTIVE COMPARATORGroup 1b Belinostat 1000 mg/m2 + CHOP
Group 2a
ACTIVE COMPARATORGroup 2a Pralatrexate 20 mg/m2 + COP
Group 2b
ACTIVE COMPARATORGroup 2b Pralatrexate 30 mg/m2 + COP
Group 3
ACTIVE COMPARATORCHOP
Interventions
Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
CHOP is the comparator arm
COP is given in combination with Pralatrexate
Eligibility Criteria
You may qualify if:
- 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:
- 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
- CD30 expression and T-cell Follicular Helper (TFH) phenotype status must be available for documentation.
- 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 (ECOG) status ≤2
- For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by:
- Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement
- Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of 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×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
- +12 more criteria
You may not qualify if:
- 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 if they can be treated with Brentuximab Vedotin (BV)
- 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 (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
- Patient with uncontrolled hypertension
- Patients status on the following:
- Has a known HIV-positive diagnosis with uncontrolled and detectable viral load
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (69)
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 District, 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)
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Uma Srinivas Atmuri, MPharm, MS
Acrotech Biopharma Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- None - Open Label
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2023
First Posted
October 10, 2023
Study Start
October 4, 2023
Primary Completion (Estimated)
July 1, 2030
Study Completion (Estimated)
November 1, 2030
Last Updated
October 23, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will not share
Data Review Committee: An Independent Data Monitoring Committee (IDMC) will be established for the purpose of reviewing patient safety and the results of the futility analysis. The IDMC will convene after the enrollment and analysis of Part 1 to evaluate safety and preliminary efficacy. The IDMC will recommend the selected dose for Belinostat and Pralatrexate. The IDMC will also convene after the analysis of 120 events, in Part 2, to state whether the study can continue. This Committee will review review study data will adjudicate tumor response and the date of onset of disease progression in all patients at the end of the study. All scans will be centrally reviewed and the primary analysis of PFS will be conducted on these results.