Integrative "Omics" Approaches for Leukemia Target Identification and Matched Therapeutic Intervention (AL-TOMICA)

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Acute Lymphoblastic; Myeloid Leukemia, Acute
• Intervention / Treatment: Biological: Functional tests; Genetic: Next Generation Sequencing analysis; Biological: Microvesicles analysis

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Benedetta Cambò, MD; Phone Number: 0521 704446; Email: bcambo@ao.pr.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • A.O.U. Bologna
    • Contact: Antonio Curti, MD; Phone Number: 051 2143680
  • Ferrara, Italy, 44124
    • Recruiting
    • A.O.U. Ferrara
    • Contact: Antonio Cuneo, MD; Phone Number: 0532 236978
  • Parma, Italy, 43126
    • Recruiting
    • AOU Parma
    • Contact: Benedetta Cambò, PHD; Phone Number: 0521 704446; Email: bcambo@ao.pr.it
  • Piacenza, Italy, 29121
    • Recruiting
    • Piacenza Hospital - AUSL Piacenza
    • Contact: Daniele Vallisa, MD; Phone Number: 0523 302242
  • Ravenna, Italy, 48121
    • Recruiting
    • Ravenna Hospital - AUSL Romagna
    • Contact: Francesco Lanza, MD; Phone Number: 0833 773899
  • Reggio Emilia, Italy, 42100
    • Recruiting
    • A.O. Reggio Emilia
    • Contact: Alessia Tieghi, MD; Phone Number: 0522 296673
  • Rimini, Italy, 47923
    • Recruiting
    • Rimini Hospital-AUSL Romagna
    • Contact: Patrizia Tosi, MD; Phone Number: 0541 705111
  • Forlì-Cesena
    • Meldola, Forlì-Cesena, Italy, 47014
      • Recruiting
      • IRST-IRCCS Meldola
      • Contact: Giovanni Martinelli, MD; Phone Number: 0543 1931094

Participation Criteria

Eligibility Criteria

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

Description

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:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Relapsed Refractory Acute Leukemias; Functional and genomics analyses will be performed on primary sample from each enrolled patient (biological preclinical study)

Biological: 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.; Genetic: 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); Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequencies of alternative therapies identified for AL patients	Number of patients treated with alternative therapies	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional and chemogenomic profiling	Dose-response curves for each drug tested, genetic profile for NGS analyses, description of vesicles contents	24 months

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria di Parma

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Acute Disease
• Other Study ID Numbers: 3070

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No