Ro Plus CHOEP as First Line Treatment Before HSCT in Young Patients With Nodal Peripheral T-cell Lymphomas

NCT02223208 | Active Not Recruiting Phase 1

• 1 other identifier: FIL_PTCL13
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 27

Brief Summary

This is a multicenter study that includes two phases:

1. 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). The dose level defined as MTD of Romidepsin will be used for the subsequent phase II study.
2. 2.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.

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

Keywords

PTCL; PTCL-NOS; AITL; ALCL

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  18 months

Secondary Outcomes (10)

• Proportion of patients reaching SCT (Phase I endpoint)

  6 months

• ORR = Overall response rate (Phase I endpoint)

  6 months

• Overall Response Rate (ORR) and Complete Response (CR)(Phase II endpoint)

  6 months

• Event free survival (EFS) (Phase II endpoint)

  18 months

• Overall survival (OS) (Phase II endpoint)

  24 months

Other Outcomes (1)

• Evaluation of response biomarkers (eg TET2 mutations)

  8 years

Study Arms (1)

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.

Drug: Ro-CHOEP-21 (PHASE I); Drug: Ro-CHOEP-21 (PHASE II)

Interventions

Ro-CHOEP-21 (PHASE I) DRUG

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)

Also known as: Romidepsin, Cyclophosphamide, Doxorubicin, Vincristin, Etoposide, Prednisone

Ro-CHOEP-21

Ro-CHOEP-21 (PHASE II) DRUG

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)

Also known as: Romidepsin, Cyclophosphamide, Doxorubicin, Vincristin, Etoposide, Prednisone

Ro-CHOEP-21

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (27)

Ospedale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, AL, 15121, Italy

Location

Policlinico S. Orsola Malpighi

Bologna, BO, 40138, Italy

Location

Spedali Civili

Brescia, BS, 26123, Italy

Location

Ospedale Businco

Cagliari, CA, 09121, Italy

Location

Azienda Ospedaliera S.Croce e Carle

Cuneo, CN, 12100, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Sede di Meldola

Meldola, FC, 47014, Italy

Location

IRCCS AOU San Martino - Clinica Ematologica

Genova, GE, 16321, Italy

Location

IRCCS AOU San Martino - UO Ematologia 1

Genova, GE, 16321, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, MI, 20122, Italy

Location

Fondazione IRCCS "Istituto Nazionale dei Tumori"

Milan, MI, 20133, Italy

Location

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Milan, MI, 20162, Italy

Location

AO Ospedali Riuniti Villa Sofia - Cervello (Presidio Cervello)

Palermo, PA, 90146, Italy

Location

IRCCS Centro di Riferimento Oncologico (CRO)

Aviano, PN, 33081, Italy

Location

AOU di Parma

Parma, PR, 43100, Italy

Location

Fondazione IRCCS - Policlinico San Matteo

Pavia, PV, 27100, Italy

Location

IRCCS Arcispedale "Santa Maria Nuova"

Reggio Emilia, RE, 42123, Italy

Location

Ospedale degli Infermi

Rimini, RN, 47900, Italy

Location

AO Città della Salute e della Scienza - Ematologia 1U

Torino, TO, 10126, Italy

Location

AO Città della Salute e della Scienza - SC Ematologia

Torino, TO, 10126, Italy

Location

AOU "Santa Maria della Misericordia"

Udine, UD, 33100, Italy

Location

Ospedale Borgo Roma

Verona, VR, 37134, Italy

Location

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

Napoli, 80131, Italy

Location

Ospedale Maggiore della Carità - SCDU Ematologia

Novara, 28100, Italy

Location

A.O. di Perugia - Santa Maria della Misericordia

Perugia, 06132, Italy

Location

Ospedale G. Da Saliceto - AUSL di Piacenza

Piacenza, 29121, Italy

Location

UO Ematologia Ospedale S.Maria delle Croci

Ravenna, 48121, Italy

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Immunoblastic Lymphadenopathy

Interventions

Clinical Trials, Phase I as Topic; romidepsin; Cyclophosphamide; Doxorubicin; Vincristine; Etoposide; Prednisone; Clinical Trials, Phase II as Topic

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Paolo Corradini, Prof

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2014
• First Posted: August 22, 2014
• Study Start: September 1, 2014
• Primary Completion: October 1, 2020
• Study Completion: February 1, 2026
• Last Updated: December 2, 2025

Record last verified: 2025-12

Locations

IT (27)