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

NCT ID: NCT02223208

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2026-02-28

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

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ro-CHOEP-21

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.

Group Type: EXPERIMENTAL

Ro-CHOEP-21 (PHASE I)

Intervention Type: 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)

Ro-CHOEP-21 (PHASE II)

Intervention Type: 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)

Interventions

Ro-CHOEP-21 (PHASE I)

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)

Intervention Type: DRUG

Ro-CHOEP-21 (PHASE II)

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)

Intervention Type: DRUG

Other Intervention Names

Romidepsin; Cyclophosphamide; Doxorubicin; Vincristin; Etoposide; Prednisone; Romidepsin; Cyclophosphamide; Doxorubicin; Vincristin; Etoposide; Prednisone

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 e ≤ 65 years

2. Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL including other nodal TFH, ALK-ALCL

3. Stage II-IV

4. Written informed consent

5. No prior treatment for lymphoma

6. No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)

7. HIV negativity

8. Absence of active hepatitis C virus (HCV) infection

9. HBV negativity or patients with HBcAb +, HBsAg -, HBs Ab+/- with HBV-DNA negativity (in these patients Lamivudine prophylaxis is mandatory)

10. Levels of serum bilirubin, alkaline phosphatase and transaminases < 2 the upper normal limit, if not disease related

11. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent

12. Ejection fraction > 50% and myocardial stroke in the last year nor QT prolongation (QTc interval < 480 msec using the Fridericia formula)

13. Clearance of creatinine > 60 ml/min if not disease related

14. Spirometry Diffusion Capacity (DLCO) > 50%

15. Absence of active, uncontrolled infection

16. 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

17. Availability of histological material for central review and pathobiological studies.

Exclusion Criteria

1. Age <18 e > 65 years

2. Hystology other than: PTCL-NOS, AITL, ALK-ALCL

3. Stage I

4. Prior treatment for lymphoma

5. Positive serologic markers for human immunodeficiency virus (HIV)

6. Active hepatitis B virus (HBV) infection

7. Active hepatitis C virus (HCV) infection

8. Levels of serum bilirubin, alkaline phosphatase and transaminases > 2 the upper normal limit, if not disease related

9. Ejection fraction < 50% and no myocardial stroke in the last year or QT prolongation (QTc interval > 480 msec using the Fridericia formula)

10. Clearance of creatinine < 60 ml/min if not disease related

11. Spirometry Diffusion Capacity (DLCO) < 50%

12. Pregnancy or lactation

13. Patient not agreeing to take adequate contraceptive measures during the study

14. Psychiatric disease that precludes understanding concepts of the trial or signing informed consent

15. Any active, uncontrolled infection

16. 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paolo Corradini, Prof

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Locations

Ospedale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Policlinico S. Orsola Malpighi

Bologna, BO, Italy

Spedali Civili

Brescia, BS, Italy

Ospedale Businco

Cagliari, CA, Italy

Azienda Ospedaliera S.Croce e Carle

Cuneo, CN, Italy

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

Meldola, FC, Italy

IRCCS AOU San Martino - Clinica Ematologica

Genova, GE, Italy

IRCCS AOU San Martino - UO Ematologia 1

Genova, GE, Italy

Istituto Clinico Humanitas

Rozzano, Milano, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, MI, Italy

Fondazione IRCCS "Istituto Nazionale dei Tumori"

Milan, MI, Italy

Azienda Ospedaliera Ospedale Niguarda Ca' Granda

Milan, MI, Italy

AO Ospedali Riuniti Villa Sofia - Cervello (Presidio Cervello)

Palermo, PA, Italy

IRCCS Centro di Riferimento Oncologico (CRO)

Aviano, PN, Italy

AOU di Parma

Parma, PR, Italy

Fondazione IRCCS - Policlinico San Matteo

Pavia, PV, Italy

IRCCS Arcispedale "Santa Maria Nuova"

Reggio Emilia, RE, Italy

Ospedale degli Infermi

Rimini, RN, Italy

AO Città della Salute e della Scienza - Ematologia 1U

Torino, TO, Italy

AO Città della Salute e della Scienza - SC Ematologia

Torino, TO, Italy

AOU "Santa Maria della Misericordia"

Udine, UD, Italy

Ospedale Borgo Roma

Verona, VR, Italy

Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale

Napoli, , Italy

Ospedale Maggiore della Carità - SCDU Ematologia

Novara, , Italy

A.O. di Perugia - Santa Maria della Misericordia

Perugia, , Italy

Ospedale G. Da Saliceto - AUSL di Piacenza

Piacenza, , Italy

UO Ematologia Ospedale S.Maria delle Croci

Ravenna, , Italy

Countries

Italy

Other Identifiers

FIL_PTCL13

Identifier Type: -

Identifier Source: org_study_id