Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches

NCT04460963 | Active Not Recruiting

• 1 other identifier: AML2220
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 5

Brief Summary

The present study will be divided into 5 phases:

1. 1.Collection of bone marrow and peripheral blood (PB) samples from AML patients at diagnosis;
2. 2.Measurement of Midregional Proadrenomedullin (MR-proADM) plasma concentrations with an Immunoluminometric Assay of newly diagnosed AML patients not affected by concomitant cardiovascular disease or sepsis.
3. 3.Analysis of exosomes and microvesicles derived from PB and bone marrow samples of AML patients and culture media collected from AML samples stimulated with ADM and/or ADM (22-52)
4. 4.Study of adrenomedullin system in leukemic stem cells (CD44+/CD38-/CD31+/Lin-) in order to define a correlated expression of ADM and ADM receptors (RAMPs, PAM) with adhesion molecules (CD31, CD38, CD44s, CD44v6), cell cycle regulatory proteins (p21, p27) and genes or molecules involved in the hematopoietic differentiation process (Cul5, CD11b, CD11c, CD66, CD14, CD15, PML-RARα)
5. 5.In vitro evaluation of ADM activity in the growth, maturation and trans-endothelial migration of blasts and/or fusion of leukemic cells with endothelial cells. To do this, leukemic cells will be alternatively cultured by using in vitro models of endosteal and vascular niches.

Conditions

Acute Myeloid Leukemia

Keywords

adrenomedullin

Outcome Measures

Primary Outcomes (1)

• Evaluation of therapeutic potential of ADM inhibition on leukaemia stem cells

  Rate estimation of the in vitro arrest of leukemic blasts proliferation by ADM inhibition.

  at 1 year

Study Arms (1)

Biological evaluation

OTHER

Adrenomedullin evaluation at diagnosis at first CR and 1 year of follow-up

Other: Adrenomedullin

Interventions

Adrenomedullin OTHER

Adrenomedullin sample evaluation

Biological evaluation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with new diagnosis of primary or secondary AML.
• Participant is willing and able to give signed written informed consent according to ICH/EU/GCP and national local laws.
• Male or Female, aged \>18 years.

You may not qualify if:

• Patients affected by concomitant cardiovascular disease , such as essential hypertension (any grade), chronic renal failure (creatinine\>1.5 mg/dL), heart failure (any NYHA class), and peripheral arterial occlusive diseases, or sepsis.
• Patients affected by HIV, B or C hepatitis.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (5)

Policlinico S. Orsola-Malpighi - Uoc Ematologia

Bologna, Italy

Location

As Dell'Alto Adige, Ospedale Centrale Di Bolzano - Ematologia E Centro Trapianto Midollo Osseo

Bolzano, Italy

Location

U.O. Oncoematologia IOV

Castelfranco Veneto, Italy

Location

Ente Ecclesiastico Casa Sollievo Della Sofferenza - Ematologia

San Giovanni Rotondo, Italy

Location

Uo Ematologia - Azienda Ulss N.2 Marca Trevigiana

Treviso, Italy

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Adrenomedullin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: July 8, 2020
• Study Start: June 9, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

IT (5)