Integrative "Omics" Approaches for Leukemia Target Identification and Matched Therapeutic Intervention

NCT ID: NCT06626893

Last Updated: 2024-10-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2025-03-01

Brief Summary

The goal of this clinical trial is to use multiple "omics" sciences to more thoroughly investigate Acute Recurrent/Refractory Leukemias (LA R/R) after conventional therapy in order to identify new targets and/or therapeutic approaches, in patients with a diagnosis of Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma B(ALL-B), Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma T (ALL-T), Acute Biphenotypic Leukemia/II as defined by WHO( World Health Organization) 2016, relapsed or refractory after at least one line of therapy. The main question that the trial aims to answer is: "Can molecules with known biological activity be active and represent possible new therapeutic strategies in relapsed/refractory Acute Leukemias on the basis of response profiles identified through the integration of next-generation chemogenomic and functional analyses? " It is expected that a minimum of 100 patients, male and female, aged 18 years and older, will be included. To participate in the study, the patient must consent to the performance on biological specimen (peripheral blood and bone marrow) of genetic/molecular and/or "omics" investigations performed with modern sequencing techniques, such as Next Generation Sequencing, Single Cell RNA Seq (scRNAseq), RT-qPCR(Quantitative reverse transcription polymerase chain reaction). These investigations will aim to improve the understanding of the genetic and molecular alterations of her disease. In addition, your cells will be used in the laboratory to perform in vitro sensitivity studies (drug response profiling - DRP) that aim to simultaneously test a set of hundreds of drugs to assess sensitivity or resistance profiles of your disease cells with the aim of identifying specific new therapies that target specific cellular mechanisms. In addition, part of the biological sample will be used for investigations of the bone marrow microenvironment and the "secretome", i.e., cell signaling molecules and methods. In order to accomplish this study, samples from peripheral or bone marrow blood taken during routine investigations performed during follow-up and re-evaluation visits for the patient's disease as per normal clinical practice will be used. Among the investigations that will be performed on the blood sample will be the genetic/molecular and/or omics and preclinical investigations described above.

Conditions

Myeloid Leukemia, Acute; Leukemia, Acute Lymphoblastic

Study Design

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

Study Groups

Relapsed Refractory Acute Leukemias

Functional and genomics analyses will be performed on primary sample from each enrolled patient (biological preclinical study)

Group Type: OTHER

Functional tests

Intervention Type: BIOLOGICAL

Functional analyses will be performed on primary sample from each enrolled patient. Isolated blast cells are cultered and incubated with a specific library of drugs (175 drugs) at four different concentrations for 72 hours.

Next Generation Sequencing analysis

Intervention Type: GENETIC

For each patient, sequencing analyses will be performed on blast cells (for somatic mutations) and on epithelial cells from buccal swab (for germline mutations)

Microvesicles analysis

Intervention Type: BIOLOGICAL

Analyses on microvesicles isolated from both Bone Marrow samples and Peripheral Blood Samples will be performed to investigate the microenvironment of the disease.

Interventions

Functional tests

Functional analyses will be performed on primary sample from each enrolled patient. Isolated blast cells are cultered and incubated with a specific library of drugs (175 drugs) at four different concentrations for 72 hours.

Intervention Type: BIOLOGICAL

Next Generation Sequencing analysis

For each patient, sequencing analyses will be performed on blast cells (for somatic mutations) and on epithelial cells from buccal swab (for germline mutations)

Intervention Type: GENETIC

Microvesicles analysis

Analyses on microvesicles isolated from both Bone Marrow samples and Peripheral Blood Samples will be performed to investigate the microenvironment of the disease.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients to be enrolled in the study must have a diagnosis of AML, B ALL/LBL, T ALL/LBL, MPAL/AUL as described by WHO 2016 classification and must complained relapsed or refractory disease after at least one line of therapy
• Ages Eligible for Study: over 18years
• Patients must have greater than 5% blasts in the bone marrow with or without extramedullary disease
• Patients with must have recurrent disease, documented by clinical or radiographic criteria, as well as histologic verification of the malignancy at original diagnosis
• Patients may be enrolled on study regardless of the timing of prior I therapy
• Patients must be capable of understanding the investigational nature and the objectives of the study. All patients must sign a written informed consent.

Exclusion Criteria

-

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

Sponsors

Azienda Ospedaliero-Universitaria di Parma

OTHER

Sponsor Role: lead

Responsible Party

Benedetta Cambò

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

IRST-IRCCS Meldola

Meldola, Forlì-Cesena, Italy

Site Status: RECRUITING

A.O.U. Bologna

Bologna, , Italy

Site Status: RECRUITING

A.O.U. Ferrara

Ferrara, , Italy

Site Status: RECRUITING

AOU Parma

Parma, , Italy

Site Status: RECRUITING

Piacenza Hospital - AUSL Piacenza

Piacenza, , Italy

Site Status: RECRUITING

Ravenna Hospital - AUSL Romagna

Ravenna, , Italy

Site Status: RECRUITING

A.O. Reggio Emilia

Reggio Emilia, , Italy

Site Status: RECRUITING

Rimini Hospital-AUSL Romagna

Rimini, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Benedetta Cambò, MD

Role: CONTACT

bcambo@ao.pr.it

0521 704446

Facility Contacts

Giovanni Martinelli, MD

Role: primary

0543 1931094

Antonio Curti, MD

Role: primary

051 2143680

Antonio Cuneo, MD

Role: primary

0532 236978

Benedetta Cambò, PHD

Role: primary

bcambo@ao.pr.it

0521 704446

Daniele Vallisa, MD

Role: primary

0523 302242

Francesco Lanza, MD

Role: primary

0833 773899

Alessia Tieghi, MD

Role: primary

0522 296673

Patrizia Tosi, MD

Role: primary

0541 705111

Other Identifiers

3070

Identifier Type: -

Identifier Source: org_study_id