Novel Therapeutic Approach for Human T-cell Malignancies

Istituto Oncologico Veneto IRCCS120 enrolled

Overview

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 Type

OBSERVATIONAL

Enrollment

120

Conditions

T-Cell Leukemia/Lymphoma, Adult

Interventions

Translation analysisOTHER

Novel strategies to selectively eliminate neoplastic T cells by modulating intracellular ROS levels.

Eligibility

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: Through study completion, an average of 2 years

Secondary Outcomes

Secondary outcome

Development of drug combinations that can selectively eliminate T-cell leukemia/lymphoma cells

Time frame: 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.

Time frame: 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.

Time frame: Through study completion, an average of 2 years

Novel Therapeutic Approach for Human T-cell Malignancies

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts