Peripheral T-cell Lymphomas (PTCL)Phase 1/2FIL_PTCL13NCT02223208
Ro Plus CHOEP as First Line Treatment Before HSCT in Young Patients With Nodal Peripheral T-cell Lymphomas
A Phase 1/2 study testing Ro-CHOEP-21 (PHASE I) and Ro-CHOEP-21 (PHASE II) in people with Peripheral T-cell Lymphomas (PTCL) and PTCL-NOS, run by Fondazione Italiana Linfomi - ETS at 27 sites in Italy.
Trial summary
This is a multicenter study that includes two phases: 1. A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose escalation of Romidepsin (8, 10, 12, 14 mg). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Peripheral T-cell Lymphomas (PTCL), PTCL-NOS, Angioimmunoblastic T-cell Lymphoma (AITL)
- What is being tested?
- Ro-CHOEP-21 (PHASE I) and Ro-CHOEP-21 (PHASE II)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 27 sitesItaly
- Study dates
- Sep 2014to 25 Mar 2026
- Phase
- Phase 1/2
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 e ≤ 65 years
- Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL including other nodal TFH, ALK-ALCL
- Stage II-IV
- Written informed consent
- No prior treatment for lymphoma
- No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
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- HIV negativity
- Absence of active hepatitis C virus (HCV) infection
- HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)
- Levels of serum bilirubin, alkaline phosphatase and transaminases < 2 the upper normal limit, if not disease related
- No psychiatric illness that precludes understanding concepts of the trial or signing informed consent
- Ejection fraction > 50% and myocardial stroke in the last year nor QT prolongation (QTc interval < 480 msec using the Fridericia formula)
- Clearance of creatinine > 60 ml/min if not disease related
- Spirometry Diffusion Capacity (DLCO) > 50%
- Absence of active, uncontrolled infection
- For males and females of child-bearing potential, agreement upon the use of effective contraceptive methods prior to study entry, for the duration of study participation and in the following 90 days after discontinuation of study treatment
- Availability of histological material for central review and pathobiological studies.
Who cannot join
- Age <18 e > 65 years
- Hystology other than: PTCL-NOS, AITL, ALK-ALCL
- Stage I
- Prior treatment for lymphoma
- Positive serologic markers for human immunodeficiency virus (HIV)
- Active hepatitis B virus (HBV) infection
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- Active hepatitis C virus (HCV) infection
- Levels of serum bilirubin, alkaline phosphatase and transaminases > 2 the upper normal limit, if not disease related
- Ejection fraction < 50% and no myocardial stroke in the last year or QT prolongation (QTc interval > 480 msec using the Fridericia formula)
- Clearance of creatinine < 60 ml/min if not disease related
- Spirometry Diffusion Capacity (DLCO) < 50%
- Pregnancy or lactation
- Patient not agreeing to take adequate contraceptive measures during the study
- Psychiatric disease that precludes understanding concepts of the trial or signing informed consent
- Any active, uncontrolled infection
- Prior history of malignancies other than PTCLs in the last five years (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast).
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
Italy27 sites
Ospedale SS. Antonio e Biagio e Cesare Arrigo
Alessandria, AL, 15121
IRCCS Centro di Riferimento Oncologico (CRO)
Aviano, PN, 33081
Policlinico S. Orsola Malpighi
Bologna, BO, 40138
Spedali Civili
Brescia, BS, 26123
Ospedale Businco
Cagliari, CA, 09121
Azienda Ospedaliera S.Croce e Carle
Cuneo, CN, 12100
IRCCS AOU San Martino - Clinica Ematologica
Genova, GE, 16321
IRCCS AOU San Martino - UO Ematologia 1
Genova, GE, 16321
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Sede di Meldola
Meldola, FC, 47014
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, MI, 20122
Fondazione IRCCS "Istituto Nazionale dei Tumori"
Milan, MI, 20133
Azienda Ospedaliera Ospedale Niguarda Ca' Granda
Milan, MI, 20162
Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
Naples, 80131
Ospedale Maggiore della Carità - SCDU Ematologia
Novara, 28100
AO Ospedali Riuniti Villa Sofia - Cervello (Presidio Cervello)
Palermo, PA, 90146
AOU di Parma
Parma, PR, 43100
Fondazione IRCCS - Policlinico San Matteo
Pavia, PV, 27100
A.O. di Perugia - Santa Maria della Misericordia
Perugia, 06132
Ospedale G. Da Saliceto - AUSL di Piacenza
Piacenza, 29121
UO Ematologia Ospedale S.Maria delle Croci
Ravenna, 48121
IRCCS Arcispedale "Santa Maria Nuova"
Reggio Emilia, RE, 42123
Ospedale degli Infermi
Rimini, RN, 47900
Istituto Clinico Humanitas
Rozzano, Milano, 20089
AO Città della Salute e della Scienza - Ematologia 1U
Torino, TO, 10126
AO Città della Salute e della Scienza - SC Ematologia
Torino, TO, 10126
AOU "Santa Maria della Misericordia"
Udine, UD, 33100
Ospedale Borgo Roma
Verona, VR, 37134
About this study
Official title: Romidepsin in Combination With CHOEP as First Line Treatment Before Hematopoietic Stem Cell Transplantation in Young Patients With Nodal Peripheral T-cell Lymphomas: a Phase I-II Study
This is a multicenter study that includes two phases:
- A phase I study to define the maximum tolerated dose (MTD) of Romidepsin in addition to CHOEP-21 and to test the safety and feasibility of CHOEP-21 in combination with dose escalation of Romidepsin (8, 10, 12, 14 mg). The dose level defined as MTD of Romidepsin will be used for the subsequent phase II study.
- A phase II study to evaluate the efficacy (response rate, progression free survival and overall survival) and safety of Ro-CHOEP-21 incorporated into a treatment strategy including SCT.
Read the detailed description
PHASE I A1) Induction phase Ro-CHOEP-21 x 3 cycles
- Romidepsin (dose escalation) starting dose: 12mg/ms iv day +1 and +8. Dose modification according to toxicity (14mg/ms day +1 and +8; 10mg/ms day +1 and +8; 8mg/ms day +1 and +8);
- CHOEP-21 (Doxorubicin 50 mg/ms iv day +1; Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1; Cyclophosphamide 750 mg/ms iv day +1; Etoposide 100mg/ms iv from day +1 to +3; Prednisone100 mg orally from days +1 to +5).
According to the response achieved after the first 3 Ro-CHOEP-21 cycles:
- PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2
- SD or PD: Treatment failures, proceed to salvage according to each institutional policy.
A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course followed by peripheral stem cell harvesting.
According to response achieved after 6 Ro-CHOEP-21 cycles:
CR: BEAM or FEAM or CEAM followed by auto-SCT PR
- Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched (class I) sibling donors. Donor selection is based on molecular high-resolution typing (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In case, no class I and class II completely identical urelated donor (10 out of 10 gene loci) can be identified, the degree of histocompatibility between patient and donor must fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic histocompatibility.
- when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.
- Haploidentical transplantation is allowed in selected cases < PR: Treatment failures, proceed to salvage according to each institutional policy.
PHASE II A1) Induction phase Ro-CHOEP-21 x 3 cycles
- Romidepsin dose according to phase I iv day +1 and +8
- Doxorubicin 50 mg/ms iv day +1,
- Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1,
- Cyclophosphamide 750 mg/ms iv day +1,
- Etoposide 100mg/ms iv from day +1 to +3
- Prednisone100 mg orally from days +1 to +5
According to the response achieved after the first 3 Ro-CHOEP-21 cycles:
- PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by phase A2
- SD or PD: Treatment failures, proceed to salvage according to each institutional policy.
A2) Stem cell mobilization and transplantation phase Response evaluation and one DHAP course followed by peripheral stem cell harvesting.
According to response achieved after 6 Ro-CHOEP-21 cycles:
CR: BEAM or FEAM or CEAM followed by auto-SCT PR
- Allogeneic SCT with HLA-identical (A, B, C, DR, DQ loci) or one antigen mismatched (class I) sibling donors. Donor selection is based on molecular high-resolution typing (4 digits) of the HLA gene loci class I (HLA-A, B, and C) and class II (DRB1, DQB1). In case, no class I and class II completely identical urelated donor (10 out of 10 gene loci) can be identified, the degree of histocompatibility between patient and donor must fulfill with the minimal degree of matching established by the Italian Bone Marrow Donor Registry: HLA-A and HLA-B antigen histocompatibility and HLA-DRB1 allelic histocompatibility.
- when a suitable donor is not available: BEAM or FEAM or CEAM followed by Auto-SCT.
- Haploidentical transplantation is allowed in selected cases < PR: Treatment failures, proceed to salvage according to each institutional policy.
- Conditions
- Peripheral T-cell Lymphomas (PTCL), PTCL-NOS, Angioimmunoblastic T-cell Lymphoma (AITL), ALK- Anaplastic Large Cell Lymphoma (ALCL), Nodal Peripheral T-Cell Lymphoma of T Follicular Helper Cell Origin
- Being tested
- Ro-CHOEP-21 (PHASE I), Ro-CHOEP-21 (PHASE II)
- Keywords
- PTCL, PTCL-NOS, AITL, ALCL
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Immunoblastic Lymphadenopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ro-CHOEP-21 (PHASE I)Drug
Also called Romidepsin, Cyclophosphamide, Doxorubicin, Vincristin
Romidepsin (dose escalation) Starting dose: 12mg/ms iv day +1 and +8
Dose modification according to toxicity:
- 14mg/ms day +1 and +8
- 10mg/ms day +1 and +8
- 8mg/ms day +1 and +8
CHOEP-21
- Doxorubicin 50 mg/ms iv day +1 or +2,
- Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2
- Cyclophosphamide 750 mg/ms iv day +1 or +2
- Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
- Prednisone100 mg orally from days +1 to +5 or from days +2 to +6
PR or CR:Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)
Ro-CHOEP-21 (PHASE II)Drug
Also called Romidepsin, Cyclophosphamide, Doxorubicin, Vincristin
Ro-CHOEP-21 x 3 cycles
- Romidepsin dose according to phase I iv day +1 and +8
- Doxorubicin 50 mg/ms iv day +1 or +2,
- Vincristin 1.4 mg/ms (maximum 2.0 mg total dose) iv day+1 or +2,
- Cyclophosphamide 750 mg/ms iv day +1 or +2
- Etoposide 100mg/ms iv from day +1 to +3 or from day +2 to +4
- Prednisone100 mg orally from days +1 to +5 or from days +2 to +6
PR or CR: Ro-CHOEP-21 for 3 additional cycles followed by stem cell mobilization and transplantation phase (CR --> AUTO-SCT, PR --> ALLO-SCT)
| Study group | Role | What they receive |
|---|---|---|
| Ro-CHOEP-21 | Experimental | During the Phase I It will administered Romidepsin (dose escalation) and the combination of CHOEP-21. During the Phase II It will administered Romidepsin (dose according to phase I) and the combination of CHOEP-21. Receives: Drug: Ro-CHOEP-21 (PHASE I); Drug: Ro-CHOEP-21 (PHASE II) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) of Ro-CHOEP-21 (Phase I endpoint)
Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non hematologic toxicity or a delay >15 days of planned cycle date observed during the first two cycles according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
Measured: 3 months
Progression Free Survival (PFS) of Ro-CHOEP-21 (Phase II endpoint)
PFS on intention to treatment (ITT) evaluated at 18 months. PFS will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause.
Measured: 18 months
Secondary outcomes (10)
Proportion of patients reaching SCT (Phase I endpoint)
Proportion of patients reaching SCT
Measured: 6 months
ORR = Overall response rate (Phase I endpoint)
Overall response rate (ORR, defined according to the Cheson 2007 response criteria) of the combination of Ro-CHOEP-21.
Measured: 6 months
Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint)
ORR and CR (defined according to the Cheson 2007 response criteria), after induction treatment and after SCT.
Measured: 6 months
Event free survival (EFS) (Phase II endpoint)
Event free survival (EFS) defined as the time between the date of enrollment and the date of discontinuation of treatment for any reason
Measured: 18 months
Overall survival (OS) (Phase II endpoint)
Overall survival (OS) defined as the time between the date of enrolment and the date of death from any cause in the ITT population enrolled in the study
Measured: 24 months
Progression Free Survival (PFS) and Overall Survival (OS) (Phase II endpoint)
PFS and OS in patients not responding to the first 3 courses of Ro-CHOEP-21
Measured: 3 months
Toxicities (Phase II endpoint)
Evaluation during the interim analyses of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
Measured: 18 months
Higher toxicities (Phase II endpoint)
Evaluation during all the pretransplant phase of any grade III or higher toxicities, recorded and classified according to the definitions of NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 (2009)
Measured: 18 months
Treatment-related mortality (TRM) (Phase II Endpoint)
Treatment-related mortality defined as any death that was not attributable to the lymphoma.
Measured: 24 months
Graft-versus-host disease (GVHD) (Phase II endpoint)
Incidence of acute and chronic GVHD in allografted patients
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionOct 2020
- Study completion25 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral T-cell Lymphomas (PTCL)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Italiana Linfomi - ETS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paolo Corradini, Prof, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02223208
- Sponsor's protocol ID
- FIL_PTCL13
- Acronym
- FIL_PTCL13
- Status last verified
- Aug 2026
- First submitted
- 21 Jul 2014
- Last updated
- 19 Aug 2026
- Results posted
- No