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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Italiana Linfomi Ets

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

1 Sep 2014 → 25 Mar 2026

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene International

External identifiers

EU CT number

2024-511639-83-00

EudraCT number

2013-005179-41

ClinicalTrials.gov

NCT02223208

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Efficacy, Therapy

Phase I: To define the maximum tolerated dose (MTD) of Ro-CHOEP-21
Phase II: To evaluate the efficacy in term of Progression Free Survival (PFS) of Ro-CHOEP-21

Secondary objectives 8

1. Fase I: To assess the feasibility of the Ro-CHOEP-21 treatment strategy combined with SCT
2. Fase II: To evaluate ORR and in particular CR rate achieved before and after SCT.
3. Phase II: To evaluate event free survival (EFS) and overall survival (OS)
4. Phase II: To evaluate the safety of treatment
5. Phase II: To evaluate the outcome of early allogeneic SCT in patients in PR at the end of induction phase
6. Phase II: To estimate the treatment-related mortality (TRM)
7. Phase II: To evaluate the incidence of acute and chronic GVHD in allografted patients
8. Phase II: To improve the knowledge on PTCL diagnosis, classification and biology.

Conditions and MedDRA coding

Anaplastic Large T-cell Lymphoma ALK negative

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. age ≥18 e ≤ 65 years
2. Peripheral T-cell lymphomas at diagnosis including: PTCL-NOS, AITL, ALK negative 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 16

1. age <18 e > 65 years
2. Hystology other than: PTCL-NOS, AITL, ALK negative 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Incidence of dose-limiting toxicity (DLT) of Ro-CHOEP-21, considering as maximum dose the one causing induction of any grade ≥ 3 non-haematological 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)
2. Phase II: 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.

Secondary endpoints 11

1. Phase I: Proportion of patients reaching SCT
2. Overall response rate (ORR, defined according to the Lugano Classification 2014 response criteria) of the combination of Ro- CHOEP-21.
3. Phase II: ORR and CR (defined according to the Lugano Classification 2014 response criteria), after Ro-CHOEP-21 and after SCT Event free survival (EFS) induction treatment and after SCT
4. Phase II: Event free survival (EFS) defined as the time between the date of enrollment and the date of discontinuation of treatment for any reason
5. Phase II: 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
6. Phase II: PFS and OS in patients not responding to the first 3 courses of Ro- CHOEP-21
7. Phase II: 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)
8. Phase II: 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)
9. Phase II. 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)
10. Phase II: Treatment-related mortality defined as any death that was not attributable to the lymphoma.
11. Phase II: Incidence of acute and chronic GVHD in allografted patients

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Italiana Linfomi Ets

Sponsor organisation

Fondazione Italiana Linfomi Ets

Address

Piazza Filippo Turati 5

City

Alexandria

Postcode

15121

Country

Italy

Scientific contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Paolo Corradini, MD

Public contact point

Organisation

Fondazione Italiana Linfomi Ets

Contact name

Paolo Corradini, MD

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications