Peripheral T Cell LymphomaPhase 3CRESCENDONCT06072131
To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
A Phase 3 study testing Belinostat Injection, Pralatrexate Injection and CHOP in people with Peripheral T Cell Lymphoma, run by Acrotech Biopharma Inc. at 58 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral T Cell Lymphoma
- What is being tested?
- Belinostat Injection, Pralatrexate Injection and CHOP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 504 participants
- Where
- 58 sitesin 10 countries
- Study dates
- 4 Oct 2023to Nov 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
- Calculated creatinine clearance of ≥ 60 mL/min
- 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:
- 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 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma)
- Calculated creatinine clearance of ≥ 60 mL/min
- UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal) and must be available for documentation.
- 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
- Patient (male or female) is at least 18 years of age at the time of informed consent
- 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.
- 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.
Who cannot join
- A patient will not be eligible for inclusion if ANY of the criteria listed below apply:
- 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
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- 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
- Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and detectable viral load or immunological evidence of chronic active disease
- Patient with central nervous system metastasis
- 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
- 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
- Patient with a known history of drug or alcohol abuse
- Pregnant or breastfeeding women
Trial locations and contacts
58 sites in 10 countries.
58 sites in 10 countries
United States10 sites
University of Colorado School of Medicine
Aurora, Colorado, 80045
University of California, San Francisco Fresno
Clovis, California, 93611
Ohio Health Research Institute
Columbus, Ohio, 43212
Henry Ford Health System
Detroit, Michigan, 48202
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Norton Cancer Institute
Louisville, Kentucky, 40207
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System Memorial Cancer Institute
Pembroke Pines, Florida, 33026
University of California, Los Angeles Hem/ Onc Clinical Research Unit, Suite 600
Santa Monica, California, 90404
Baylor Scott & White Medical Center - Temple
Temple, Texas, 76508
Italy9 sites
Azienda Ospedaliera SS. Antonio e Biagio e C. Arrigo
Alessandria
Policlinico GB Rossi Borgo Roma
Borgo Roma, Verona, 37134
Ospedale Policlinico San Martino, IRCCS
Genova, 16132
Servizio Sanitario Regionale Emilia-Romagna-Istituto Scientifico Romagnolo per lo Studio dei Tumori "Dino Amadori" Srl (IRST)
Meldola, Province Of Forlì-Cesena, 47014
University of Milano Bicocca
Milan, Bicocca, 20126
Azienda Ospedaliera Universitaria di Parma
Parma, 43126
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Azienda USL di Ravenna
Ravenna, 41800
Azienda Ospedaliera Cardinale Giovanni Panico
Tricase, Apulia, 73039
Spain9 sites
Hospital del Mar Medical Research Institute
Barcelona, 08003
ICO - Hospital Duran i Reynals
Barcelona, 08908
Hospital Universitario Basurto
Bilbao, Bizkaia, 48013
Clinica Universidad de Navarra - Madrid
Madrid, 28027
Hospital Universitario Fundación Jiménez Díaz
Moncloa-Aravaca, Madrid, 28040
Hospital Universitario de Navarra
Pamplona, Navarre, 31008
Clinica Universidad de Navarra
Pamplona, 31008
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitario y Politecnico La Fe
Valencia, 46026
South Korea8 sites
Inje University Busan Paik Hospital
Busan, Busanjin District
Yeungnam University Medical Center
Daegu, Nam-gu
Gachon University Gil Medical Center
Incheon, 21565
Seoul National University Hospital
Seoul
Severance hospital, Yonsei University
Sinchon-dong, Seoul
Asan Medical Center
Songpa-dong, Seoul, 05505
Ajou University Hospital
Suwon, Gyenoggi-do, 16499
The Catholic University of Korea - St. Vincents Hospital
Suwon, Gyeonggi-do
Turkey (Türkiye)6 sites
Adana City Education and Research Hospital
Adana, 4522
Ankara University Medical Faculty Hospital
Altındağ, Ankara, 06230
Ege Univ. Hospital
Bornova, 35100
Bilkent University
Çankaya, Ankara, 06800
VKV AMERICAN HOSPITAL, Medical Oncology Outpatient Clinic
Şişli, Istanbul, 34365
Gazi University Faculty of Medicine
Yenimahalle, Ankara, 06560
Hungary5 sites
Semmelweis Egyetem
Budapest, 1088
National Institute of Oncology
Budapest, 1122
University of Debrecen Clinical Center
Debrecen, Nagyerdei Krt. 98, 4032
Andras Josa University Teaching Hospital
Nyíregyháza, Szent Istvan Utca, 68
Belgyogyaszati Klinika es Kardiologiai Kozpont
Szeged, 6725
Poland4 sites
Pratia MCM Krakow
Krakow, 30-727
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
Lodz, Łódź Voivodeship, 93-513
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw
University Hospital in Wroclaw
Wroclaw, Wroclaw, 50-367
Taiwan3 sites
Chang Bing Show Chwan Memorial Hospital
Changhua, 505
Hematology Oncology Taipei Medical University - Shuang-Ho Hospital
New Taipei City
National Cheng Kung University Hospital NCKUH
Tainan, Southern Taiwan, 704
Canada2 sites
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, M5G 2C4
Germany2 sites
Universitatsmedizin Gottingen
Göttingen, 37075
Universitaetsklinikum Halle (Saale)
Halle, 06120
About this study
Official title: 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
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.
Read the 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:
- Group 1a (Bel-CHOP) Belinostat 600 mg/m2
- Group 1b (Bel-CHOP) Belinostat 1000 mg/m2
- Group 2a (Fol-COP) Pralatrexate 20 mg/m2
- Group 2b (Fol-COP) Pralatrexate 30 mg/m2
- 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
- Conditions
- Peripheral T Cell Lymphoma
- Being tested
- Belinostat Injection, Pralatrexate Injection, CHOP, COP
- Medical subject headings
- Lymphoma, T-Cell, Peripheral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belinostat InjectionDrug
Also called Beleodaq®
Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Pralatrexate InjectionDrug
Also called Folotyn®
Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
CHOPDrug
Also called Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisone
CHOP is the comparator arm
COPDrug
Also called Cyclophosphamide, Oncovin (vincristine), and Prednisone
COP is given in combination with Pralatrexate
| Study group | Role | What they receive |
|---|---|---|
| Group 1a | Active comparator | Group 1a Belinostat 600 mg/m2 + CHOP Receives: Drug: Belinostat Injection; Drug: CHOP |
| Group 1b | Active comparator | Group 1b Belinostat 1000 mg/m2 + CHOP Receives: Drug: Belinostat Injection; Drug: CHOP |
| Group 2a | Active comparator | Group 2a Pralatrexate 20 mg/m2 + COP Receives: Drug: Pralatrexate Injection; Drug: COP |
| Group 2b | Active comparator | Group 2b Pralatrexate 30 mg/m2 + COP Receives: Drug: Pralatrexate Injection; Drug: COP |
| Group 3 | Active comparator | CHOP Receives: Drug: CHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progression-free survival is determined from randomization to the first documented Progression of Disease or death, whichever occurs first.
Measured: 4.5 years
Secondary outcomes (1)
Overall survival
It is the time from randomization to the death
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start4 Oct 2023
- Primary completionJul 2030 (estimated)
- Study completionNov 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral T Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 504 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Uma Srinivas Atmuri, MPharm, MS, Study director, Acrotech Biopharma Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06072131
- Sponsor's protocol ID
- SPI-Bel-301 Study
- Other IDs
- 70,789
- Acronym
- CRESCENDO
- Status last verified
- Oct 2026
- First submitted
- 19 Sep 2023
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.