Chemogenomic Profiling in Hematological Malignancies (HEM-Profiling 2021)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 250
- Locations
- 1
- Primary Endpoint
- To evaluate the anti-cancer activity of bio-active compounds and derivatives present in FDA/EMA approved or investigator provided libraries, investigational molecules
Study Overview
Brief Summary
The study will be conducted retrospectively and prospectively, using bone marrow (BM) or peripheral blood (PB) samples or biopsies of lymph nodes or tissues with metastatic involvement taken from previously stored samples here at the University Hospital of Parma or taken from patients that need to underwent diagnostic evaluation for a suspect or a defined diagnosis of hematological malignancies collected at the University Hospital of Parma.
Detailed Description
The hematological malignancies are referred to all the different hematological entities according to WHO 2016 Classification such as acute (AML, ALL) or chronic leukemia (CLL, CML, HCL), myeloproliferative or lymphoproliferative disorders (MF, PV, TE, CMML, NHL, HL) and myelodysplastic or myelodysplastic/myeloproliferative disorders.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 1 Year to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient aged >1 year old, referred for evaluation to the University Hospital of Parma;
- •Retrospective study: previously patients with hematological malignancies;
- •Prospective study: 1) patients with clinical suspect of hematological malignancies which requires a diagnostic assessment using peripheral blood drawn, bone marrow aspirate/biopsy, lymph nodes biopsies or biopsies of tissues with metastatic involvement including liquor from rachicentesis, tissue aspirate etc. 2) patients with clinical suspect of relapsed/refractory onco-hematological disorder, which requires a diagnostic assessment using bone marrow aspirate/biopsy or biopsies of tissues with metastatic involvement including lymph nodes, liquor from rachicentesis, tissue aspirate etc. 3) patients that progress in blastic transformation from a chronic condition or suspect of relapsed/refractory hematological disease, which requires a diagnostic assessment using peripheral blood drawn, bone marrow aspirate/biopsy, lymph nodes biopsies or biopsies of tissues with metastatic involvement including liquor from rachicentesis, tissue aspirate etc;
- •Written informed consent. Retrospective study: informed consent will be signed during the first follow-up visit.
Exclusion Criteria
- •Age <1 year old
- •Patients who are unable to provide informed consent prior to any procedure for any reason.
Arms & Interventions
Hematological malignancies
Patients with hematological malignancies either treatment free or relapsed/ refractory
Intervention: Genetic, molecular and/or omics analyses (Other)
Outcomes
Primary Outcomes
To evaluate the anti-cancer activity of bio-active compounds and derivatives present in FDA/EMA approved or investigator provided libraries, investigational molecules
Time Frame: At baseline
The study will be performed in malignant cells of a cohort of 250 patients with onco-hematological disorders obtained from a bone marrow aspirate/biopsy or biopsies of tissues with metastatic involvement including lymph nodes, liquor from rachicentesis, tissue aspirate etc. separated by a tissue-specific protocol: densitometry protocol for peripheral or bone marrow blood, tissue fractionation for tissue biopsies, precipitation for liquor. Cells will be than cultured in the presence or absence of small molecules derived from chemical library FDA/EMA approved, investigational molecules (monoclonal antibodies, antibody-drug conjugate, other experimental compounds). We will use miniaturized assays such cell culture in 384 multiwell plates to maximize the use of primary cells and to test simultaneously multiple concentrations of multiple drugs. We will perform several assays to assess cellular response to drug's perturbation such as: proliferation, cell cycle and apoptosis analysis
To characterize molecular biomarkers for the identification of novel target therapies
Time Frame: At baseline
Thanks to genetic and molecular and/or omics analyses performed with new technologies (Nanostring, NGS, single cell technologies, radiomics), we propose to study novel molecular target that may be sensitive to the tested compounds in order to identify new target therapies.
Correlate anti-cancer response with diagnostic (WHO classification) and molecular or novel omics features including cytogenetics, genomics, next generation or single cell technologies, radiomics.
Time Frame: At baseline
The completion of experiments described in aim 1 will give us the opportunity, for example, to extrapolate the IC50 (half maximal inhibitory concentration: a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function) dose for a small molecule of interest and correlate this value with clinical, cytogenetic, genomic and molecular features of that particular case. These data will be further compared with larger repository publicly available in the literature.
Secondary Outcomes
No secondary outcomes reported
Investigators
Giovanni Roti
Full Professor
University of Parma