Integrative "Omics" Approaches for Leukemia Target Identification and Matched Therapeutic Intervention
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Functional tests, Next Generation Sequencing analysis, Microvesicles analysis.
- Who it may be relevant to
- Registry conditions: Myeloid Leukemia, Acute, Leukemia, Acute Lymphoblastic. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- 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.
Primary outcome measures
- Frequencies of alternative therapies identified for AL patients [Time frame: 12 months]
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
\-
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
Italy · 8 centers
- IRST-IRCCS Meldola — Meldola
- A.O.U. Bologna — Bologna
- A.O.U. Ferrara — Ferrara
- AOU Parma — Parma
- Piacenza Hospital - AUSL Piacenza — Piacenza
- Ravenna Hospital - AUSL Romagna — Ravenna
- A.O. Reggio Emilia — Reggio Emilia
- Rimini Hospital-AUSL Romagna — Rimini
Identifiers
NCT: NCT06626893 · 3070