Clinical trial • Phase II/III • Oncology

PRALATREXATE for Peripheral T-cell lymphoma

Phase II/III trial of PRALATREXATE for Peripheral T-cell lymphoma.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Peripheral T-cell lymphoma
Trial Stage
Phase II/III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
27-03-2024
First CTIS Authorization Date
22-07-2024

Trial design

Randomised, open-label, chop regimen (comparator arm): cyclophosphamide; doxorubicin; vincristine (vincristine sulfate); prednisone. specific per-arm doses/schedule not specified in ctis record.-controlled, adaptive Phase II/III trial in Italy, Germany, Hungary and others.

Randomised
Yes
Open Label
Yes
Comparator
CHOP regimen (comparator arm): Cyclophosphamide; Doxorubicin; Vincristine (Vincristine sulfate); Prednisone. Specific per-arm doses/schedule not specified in CTIS record.
Adaptive
True, Part 1 is a Dose Finding stage to select which of two dose levels for Belinostat and Pralatrexate associated with CHOP is best suitable for Part 2 based on safety and ORR at 3 months (dose-finding/adaptive selection).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
354

Eligibility

Recruits 354 Vulnerable population selected. Enrollment limited to adults: "Patient (male or female) is at least 18 years of age at the time of informed consent"; patients "must be willing and capable of giving written informed consent". Assent is not applicable as only adults (≥18) are eligible..

Pregnancy Exclusion
Pregnant or breastfeeding women
Vulnerable Population
Vulnerable population selected. Enrollment limited to adults: "Patient (male or female) is at least 18 years of age at the time of informed consent"; patients "must be willing and capable of giving written informed consent". Assent is not applicable as only adults (≥18) are eligible.

Inclusion criteria

  • {"criterion_text":"- 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 WHO classification, may be included. This information should be available for eligibility: a. Pathology subtype: o Peripheral T-cell lymphoma, not otherwise specified o Angioimmunoblastic T-cell lymphoma o 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. o Follicular T-cell lymphoma o 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 b. 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 local Investigator (Appendix 3) 3. Patient has an Eastern Cooperative Oncology Group (ECOG) 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 or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement b. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement 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×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) e. 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: a. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement b. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement 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 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) e. 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 (Please refer to Appendix 4 for contraception guidance). 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. Please refer to Appendix 4 for further details."}

Exclusion criteria

  • {"criterion_text":"- 1. Patients with a diagnosis of: a. Precursor T-cell lymphoma or leukemia b. Adult T-cell lymphoma/leukemia c. T-cell prolymphocytic leukemia d. T-cell large granular lymphocytic leukemia e. Primary cutaneous type ALCL f. Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) g. ALCL if they can be treated with Brentuximab Vedotin (BV) 2) Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week before dosing 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 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 status on the following: a) Has a known HIV-positive diagnosis with uncontrolled and detectable viral load b) 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"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint is PFS, defined as the time (months) from randomization to the first documented PD or death, whichever occurs first.","definition_or_measurement_approach":"The primary endpoint is PFS, defined as the time (months) from randomization to the first documented PD or death, whichever occurs first."}

Secondary endpoints

  • {"endpoint_text":"- • Overall survival is defined as time from randomization to death due to any cause. Overall survival will be censored at the date patients were last known to be alive. • Objective response rate is defined as the percentage of patients who have a CR or PR as their best objective response. • Treatment compliance- Dose delays and reduction of the treatment arms will be evaluated.","definition_or_measurement_approach":"Overall survival: time from randomization to death due to any cause (censored at last known alive date). Objective response rate: percentage of patients with CR or PR as best response. Treatment compliance: evaluation of dose delays and dose reductions in treatment arms."}

Recruitment

Planned Sample Size
354
Recruitment Window Months
44
Consent Approach
Written informed consent required: "Patient must be willing and capable of giving written informed consent". Only adults (≥18) eligible. Subject information and informed consent form documents are provided (multiple ICF documents listed).

Geography

Total Number Of Sites
37
Total Number Of Participants
145

Italy

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
25-03-2025
Processing Time Days
263
Number Of Sites
11
Number Of Participants
31

Sites

Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Hematology
Principal Investigator Name
Gerardo Musuraca
Principal Investigator Email
Gerardo.musuraca@irst.emr.it
Contact Person Name
Gerardo Musuraca
Contact Person Email
Gerardo.musuraca@irst.emr.it
Site Name
Azienda Ospedaliero Universitaria Parma
Department Name
Hematology and CTMO Unit
Principal Investigator Name
Caterina Plenteda
Principal Investigator Email
cplenteda@ao.pr.it
Contact Person Name
Caterina Plenteda
Contact Person Email
cplenteda@ao.pr.it
Site Name
Azienda Ospedaliero-Universitaria Ss Antonio E Biagio E Cesare Arrigo
Department Name
Hematology
Principal Investigator Name
Manuela Zanni
Principal Investigator Email
manuela.zanni@ospedale.al.it
Contact Person Name
Manuela Zanni
Contact Person Email
manuela.zanni@ospedale.al.it
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
CTMO-Hematology
Principal Investigator Name
Angelo Andreini
Principal Investigator Email
angelo.andreini@univr.it
Contact Person Name
Angelo Andreini
Contact Person Email
angelo.andreini@univr.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
OncoHematology
Principal Investigator Name
Monica Tani
Principal Investigator Email
monica.tani@auslromagna.it
Contact Person Name
Monica Tani
Contact Person Email
monica.tani@auslromagna.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
Hematology
Principal Investigator Name
Carlo Gambacorti Passerini
Principal Investigator Email
carlo.gambacorti@unimib.it
Contact Person Name
Carlo Gambacorti Passerini
Contact Person Email
carlo.gambacorti@unimib.it
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
OncoHematology
Principal Investigator Name
Caterina Patti
Principal Investigator Email
k.patti@villasofia.it
Contact Person Name
Caterina Patti
Contact Person Email
k.patti@villasofia.it
Site Name
Pia Fondazione Di Culto E Religione Card G Panico
Department Name
Hematology
Principal Investigator Name
Vincenzo Pavone
Principal Investigator Email
enzopavone@libero.it
Contact Person Name
Vincenzo Pavone
Contact Person Email
enzopavone@libero.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Hematology
Principal Investigator Name
Paolo Corradini
Principal Investigator Email
paolo.corradini@unimi.it
Contact Person Name
Paolo Corradini
Contact Person Email
paolo.corradini@unimi.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
Hematology
Principal Investigator Name
Adalberto Ibatici
Principal Investigator Email
Adalberto.ibatici@hsanmartino.it
Contact Person Name
Adalberto Ibatici
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
Hematology
Principal Investigator Name
Luca Arcaini
Principal Investigator Email
l.arcaini@smatteo.pv.it
Contact Person Name
Luca Arcaini
Contact Person Email
l.arcaini@smatteo.pv.it

Germany

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
242
Number Of Sites
3
Number Of Participants
35

Sites

Site Name
Universitaetsmedizin Goettingen
Department Name
Department of Hematology and Medical Oncology
Principal Investigator Name
Raphael Koch
Principal Investigator Email
raphael.koch@med.uni-goettingen.de
Contact Person Name
Raphael Koch
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Department of Hematology and Oncology
Principal Investigator Name
Niklas Gebauer
Principal Investigator Email
niklas.gebauer@uksh.de
Contact Person Name
Niklas Gebauer
Contact Person Email
niklas.gebauer@uksh.de
Site Name
Universitaetsklinikum Halle (Saale) AöR
Department Name
Department of Hematology and Medical
Principal Investigator Name
Thomas Weber
Principal Investigator Email
thomas.weber@uk-halle.de
Contact Person Name
Thomas Weber
Contact Person Email
thomas.weber@uk-halle.de

Hungary

Earliest CTIS Part Ii Submission Date
03-07-2024
Latest Decision Or Authorization Date
04-03-2025
Processing Time Days
244
Number Of Sites
7
Number Of Participants
22

Sites

Site Name
University Of Debrecen
Department Name
Egeszsegugyi Szolgaltato Egysegek, Klinikak, Belgyogyaszati Klinika
Principal Investigator Name
Arpad Illes
Principal Investigator Email
illes.arpad@med.unideb.hu
Contact Person Name
Arpad Illes
Contact Person Email
illes.arpad@med.unideb.hu
Site Name
Semmelweis University
Department Name
Belgyogyaszati és Hematologiai Klinika
Principal Investigator Name
Zsolt Nagy
Principal Investigator Email
nagy.zsolt@med.semmelweis-univ.hu
Contact Person Name
Zsolt Nagy
Site Name
Fejer Varmegyei Szent Gyoergy Egyetemi Oktato Korhaz
Department Name
BELGYOGYASZAT - III. BELGYOGYASZAT, HEMATOLOGIAI OSZTALY
Principal Investigator Name
Arpad Szomori
Principal Investigator Email
szomoriarpad@gmail.com
Contact Person Name
Arpad Szomori
Contact Person Email
szomoriarpad@gmail.com
Site Name
Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz
Department Name
Nyiregyhazi Josa Andras Tagkorhaz Haematologia
Principal Investigator Name
Laszlo Rejto
Principal Investigator Email
lrejto@med.unideb.hu
Contact Person Name
Laszlo Rejto
Contact Person Email
lrejto@med.unideb.hu
Site Name
Orszagos Onkologiai Intezet
Department Name
GYOGYSZERTERAPIAS KOZPONT HEMATOLOGIA ES LYMPHOMA OSZTALY "KEMOTERAPIA A"
Principal Investigator Name
Andras Masszi
Principal Investigator Email
masszi.andras@oncol.hu
Contact Person Name
Andras Masszi
Contact Person Email
masszi.andras@oncol.hu
Site Name
Heves Varmegyei Markhot Ferenc Oktatokorhaz Es Rendelointezet
Department Name
Belgyogyaszati-Infektologiai Centrum - BIC Belgyogyaszati Osztaly
Principal Investigator Name
Balazs Tajti
Principal Investigator Email
tajtibalazs1985@gmail.com
Contact Person Name
Balazs Tajti
Contact Person Email
tajtibalazs1985@gmail.com
Site Name
University Of Szeged
Department Name
Szent Gyorgyi Albert Klinikai Kozpont - II. sz. Belgyogyaszati Klinika es Kardiologiai Kozpont
Principal Investigator Name
Zita Borbenyi
Principal Investigator Email
borbenyizita@gmail.com
Contact Person Name
Zita Borbenyi
Contact Person Email
borbenyizita@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
02-07-2024
Latest Decision Or Authorization Date
03-03-2025
Processing Time Days
244
Number Of Sites
5
Number Of Participants
22

Sites

Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Hematologii Ogólnej
Principal Investigator Name
Tadeusz Robak
Principal Investigator Email
robaktad@csk.umed.lodz.pl
Contact Person Name
Tadeusz Robak
Contact Person Email
robaktad@csk.umed.lodz.pl
Site Name
Pratia S.A.
Principal Investigator Name
Wojciech Jurczak
Principal Investigator Email
wojciech.jurczak@pratia.com
Contact Person Name
Wojciech Jurczak
Contact Person Email
wojciech.jurczak@pratia.com
Site Name
Specjalistyczny Szpital Onkologiczny Nu-Med Sp. z o.o.
Principal Investigator Name
Ewa Chmielowska
Principal Investigator Email
ewa.chmielowska@nu-med.pl
Contact Person Name
Ewa Chmielowska
Contact Person Email
ewa.chmielowska@nu-med.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Nowotworów Układu Chłonnego
Principal Investigator Name
Joanna Romejko-Jarosińska
Principal Investigator Email
joanna.romejko-jarosinska@pib-nio.pl
Contact Person Name
Joanna Romejko-Jarosińska
Site Name
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Department Name
Klinika Hematologii, Terapii Komorkowych i Chorob Wewnetrznych
Principal Investigator Name
Anna Czyż
Principal Investigator Email
aczyz@onet.eu
Contact Person Name
Anna Czyż
Contact Person Email
aczyz@onet.eu

Spain

Earliest CTIS Part Ii Submission Date
04-07-2024
Latest Decision Or Authorization Date
17-10-2025
Processing Time Days
470
Number Of Sites
11
Number Of Participants
35

Sites

Site Name
Hospital Unviersitario Miguel Servet
Department Name
Hematology
Principal Investigator Name
Araceli Rubio Martinez
Principal Investigator Email
arubiom@salud.aragon.es
Contact Person Name
Araceli Rubio Martinez
Contact Person Email
arubiom@salud.aragon.es
Site Name
Clinica Universidad De Navarra
Department Name
Hematology
Principal Investigator Name
Miguel Angel Canales Albendea
Principal Investigator Email
macanales@unav.es
Contact Person Name
Miguel Angel Canales Albendea
Contact Person Email
macanales@unav.es
Site Name
Institut Catala D'oncologia
Department Name
Hematology
Principal Investigator Name
Eva Domingo Domenech
Principal Investigator Email
edomingo@iconcologia.net
Contact Person Name
Eva Domingo Domenech
Contact Person Email
edomingo@iconcologia.net
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Hematology
Principal Investigator Name
Rafael Andreu Lapiedra
Principal Investigator Email
andreu_raflap@gva.es
Contact Person Name
Rafael Andreu Lapiedra
Contact Person Email
andreu_raflap@gva.es
Site Name
Hospital Universitario Basurto
Department Name
Hematology
Principal Investigator Name
Maria Cristina de Barrenetxea Lekue
Contact Person Name
Maria Cristina de Barrenetxea Lekue
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Hematology
Principal Investigator Name
Sergio Ramos Cillan
Principal Investigator Email
sergio.ramos@startmadrid.com
Contact Person Name
Sergio Ramos Cillan
Contact Person Email
sergio.ramos@startmadrid.com
Site Name
Hospital Universitario De Salamanca
Department Name
Hematology
Principal Investigator Name
Norma Gutiérrez Gutiérrez
Principal Investigator Email
ncgutierrez@saludcastillayleon.es
Contact Person Name
Norma Gutiérrez Gutiérrez
Site Name
Hospital Universitario De Navarra
Department Name
Hematology
Principal Investigator Name
Jose Maria Arguiñano Perez
Principal Investigator Email
jm.arguinano.perez@navarra.es
Contact Person Name
Jose Maria Arguiñano Perez
Contact Person Email
jm.arguinano.perez@navarra.es
Site Name
Clinica Universidad De Navarra (Madrid address)
Department Name
Hematology
Principal Investigator Name
Miguel Angel Canales Albendea
Principal Investigator Email
macanales@unav.es
Contact Person Name
Miguel Angel Canales Albendea
Contact Person Email
macanales@unav.es
Site Name
Hospital Del Mar
Department Name
Hematology
Principal Investigator Name
Blanca Sánchez González
Principal Investigator Email
97894@parcdesalutmar.cat
Contact Person Name
Blanca Sánchez González
Contact Person Email
97894@parcdesalutmar.cat
Site Name
Hospital Universitario Miguel Servet (additional listing)
Department Name
Hematology
Principal Investigator Name
Araceli Rubio Martinez
Principal Investigator Email
arubiom@salud.aragon.es
Contact Person Name
Araceli Rubio Martinez
Contact Person Email
arubiom@salud.aragon.es

Sponsor

Primary sponsor

Full Name
Acrotech Biopharma Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Syneos Health France S.A.R.L.
Responsibilities
PD Central Lab; other sponsor duties
Name
Syneos Health Inc.
Responsibilities
Multiple sponsor/CRO responsibilities (codes 1,2,5,8,9,11,12,13)
Name
You V Research Private Limited
Responsibilities
Local trial conduct roles (codes 6,7)
Name
PCI Pharma Services Germany GmbH
Responsibilities
EU Qualified Person (QP) Release; other supply/packaging responsibilities
Name
Median Technologies
Responsibilities
Central Imaging Review
Name
Viedoc Technologies AB
Responsibilities
eClinical/eCRF platform roles (codes 3,7)

Third parties

  • {"country":"France","full_name":"Syneos Health France S.A.R.L.","duties_or_roles":"PD Central Lab; role code 4 (unspecified)","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Median Technologies","duties_or_roles":"Central Imaging Review","organisation_type":"Pharmaceutical company"}
  • {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"roles with codes 3 and 7 (unspecified)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"India","full_name":"You V Research Private Limited","duties_or_roles":"roles with codes 6 and 7 (unspecified)","organisation_type":"Pharmaceutical company"}
  • {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"PK Central Lab; role code 4 (unspecified)","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"role code 14; EU Qualified Person (QP) Release; PD role (code 15)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Multiple roles (codes 1,11,12,13,2,5,8,9) - various sponsor/CRO activities (as listed)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Pralatrexate
Active Substance
PRALATREXATE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
prodAuthStatus: 1
Orphan Designation
Yes
Maximum Dose
30 mg/m2
Investigational Product Name
Belinostat
Active Substance
BELINOSTAT
Modality
Small molecule
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
prodAuthStatus: 1
Orphan Designation
Yes
Maximum Dose
1000 mg/m2
Combination Treatment
Yes

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