Novel Therapeutic Approach for Human T-cell Malignancies

Identification of Targetable Vulnerabilities in Redox Homeostasis Pathways as a Novel Therapeutic Approach for Human T-cell Malignancies

This multicenter translational study, with prospective and retrospective samples, aims to identify new strategies to selectively eliminate neoplastic T cells by modulating intracellular ROS levels.

Interactions between drugs capable of activating the apoptotic process (e.g., Venetoclax) and drugs capable of altering ROS homeostasis (e.g., inhibitors of the enzyme glucose-6-phosphate dehydrogenase) will be examined.

The most promising compounds will be selected based on results obtained in vitro on cell lines and PDX already available in the laboratory, and then will be assayed ex vivo in cells obtained from patients with resistant/refractory T-cell neoplasms.

Study Overview

• Status: Recruiting
• Conditions: T-Cell Leukemia/Lymphoma, Adult
• Intervention / Treatment: Other: Translation analysis

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Michele Gottardi, MD; Phone Number: +39 0423732336; Email: michele.gottardi@iov.veneto.it
• Study Contact Backup: Name: GianLuca De Salvo, MD; Phone Number: +390498215704; Email: gianluca.desalvo@iov.veneto.it

Study Locations

• Italy
  • Napoli, Italy, 80100
    • Recruiting
    • Istituto Nazionale Tumori Fondazione G.Pascale
    • Contact: Antonio Pinto, MD; Phone Number: 081/1777-0368; Email: a.pinto@istitutotumori.na.it
  • Padua, Italy, 35128
    • Recruiting
    • Istituto Oncologico Veneto
    • Contact: Michele Gottardi, MD; Phone Number: +39 0423-732336; Email: michele.gottardi@iov.veneto.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Up to a maximum of 120 patients (both retrospective and prospective) are expected to be enrolled during the study period. Specifically, a maximum of 40 patients will be enrolled for each of the following diseases: T-cell lymphoblastic leukemias (T-ALL); T-cell non-Hodgkin lymphomas (T-NHL); NK-cell neoplasms. For retrospective peripheral blood samples, bone marrow aspirates, and lymph node biopsies, which are available at the centers involved in the study, patients will be contacted again to ask for consent regarding this project.

No additional clinical procedures are specifically required by participation in the present study. In fact, samples will be obtained from the material left over from samples taken for clinical procedures.

Description

Inclusion Criteria:

• Patients with pre- and post-thymic T-cell leukemia/lymphoma
• Patients of both sexes
• Age of patients older than 18 years
• Patient is willing to provide written and signed informed consent for participation in the study

Exclusion Criteria:

-Serious illness or medical condition that does not allow the patient to be managed according to standard treatment protocols, including uncontrolled active infection.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome	Response of leukemic cells to treatments that remodulate redox state and apoptosis from a molecular point of view, ex vivo,through the development of a multidimensional approach aimed at reducing the chemoresistance of T neoplasms	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary outcome	Development of drug combinations that can selectively eliminate T-cell leukemia/lymphoma cells	Through study completion, an average of 2 years
Secondary outcome	Analysis of DNA, RNA, protein, and circulating markers of alterations present at baseline in patient samples; profiles obtained will be correlated with response to drug treatments in order to identify biomarkers predictive of response to treatment.	Through study completion, an average of 2 years
Secondary outcome	Analysis of the efficacy of new drug combinations in vivo through the generation of PDX-based experimental mouse models derived from patients with T-cell malignancies.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Istituto Oncologico Veneto IRCCS
• Collaborators: Istituto Nazionale Tumori IRCSS-Fondazione G.Pascale

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: September 11, 2024
• First Submitted That Met QC Criteria: September 16, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: apoptosis; ROS; T-cell lymphoblastic leukemias (T-ALL); T-cell non-Hodgkin's lymphomas (T-NHL); NK cell neoplasia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: ROSinTALL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No