Targeting Pathogenic Myelopoiesis in Pancreatic Cancer

NCT07765316 | Not Yet Recruiting

• 1 other identifier: PaMPa
• Study Type: observational
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

This prospective observational study aims to investigate pathogenic myelopoiesis in patients with pancreatic ductal adenocarcinoma (PDAC) and to characterize the systemic immune alterations associated with tumor-related inflammation. The study will enroll 50 patients with newly diagnosed, non-metastatic, treatment-naïve PDAC and 50 age-matched control patients with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy. Control patients will be matched to PDAC patients by age within a range of ±5 years whenever feasible. A single peripheral blood sample will be collected at baseline from all participants. In PDAC patients, blood collection will be performed before initiation of any anti-tumor treatment. Translational analyses will characterize circulating myeloid cells, progenitor cells, and hematopoietic stem and progenitor cell-related transcriptional programs using high-dimensional flow cytometry and single-cell transcriptomic analyses. The primary objective is to identify the molecular drivers of pathogenic myelopoiesis in PDAC by assessing quantitative and qualitative differences between PDAC patients and age-matched controls in circulating myeloid and progenitor cell populations and their transcriptional profiles. The study will specifically explore the hypothesis that IL-1β-associated tumor inflammation contributes to systemic reprogramming of hematopoietic progenitor compartments and promotes myeloid-biased hematopoiesis. PDAC patients will also be followed clinically for 12 months using data derived from routine clinical practice to explore associations between baseline pathogenic myelopoiesis-related profiles and subsequent clinical outcomes. No follow-up is required for control patients.

Conditions

Pancreatic Diseases

Keywords

Pancreatic Ductal Adenocarcinoma; Pathogenic Myelopoiesis; Single-Cell Transcriptomics; High-Dimensional Flow Cytometry

Outcome Measures

Primary Outcomes (2)

• Frequency and phenotype of circulating myeloid and progenitor cell populations

  Quantitative and phenotypic differences in circulating myeloid and progenitor cell populations between treatment-naïve PDAC patients and age-matched control patients, assessed by high-dimensional flow cytometry

  Baseline, prior to initiation of anti-tumor treatment

• Transcriptional profiles of circulating myeloid cells and hematopoietic stem and progenitor cells

  Differences in transcriptional profiles of circulating myeloid cells and hematopoietic stem and progenitor cells (HSPCs) between treatment-naïve PDAC patients and age-matched control patients, including differentially expressed genes, gene ontology annotations, and gene regulatory networks.

  Baseline, prior to initiation of anti-tumor treatment

Secondary Outcomes (1)

• IL-1β-associated transcriptional signatures in circulating monocytes

  Baseline, prior to initiation of anti-tumor treatment

Study Arms (2)

Treatment-naïve PDAC patients

Adults with newly diagnosed, non-metastatic pancreatic ductal adenocarcinoma (PDAC), enrolled before initiation of chemotherapy, radiotherapy, or immunotherapy. Participants will undergo a single 14 mL peripheral blood collection at baseline, prior to any anti-tumor treatment, for translational analyses including high-dimensional flow cytometry and single-cell transcriptomic profiling. Clinical follow-up data will be collected from routine clinical practice for 12 months

Age-matched IPMN control patients

Adults with intraductal papillary mucinous neoplasm (IPMN) under surveillance and no evidence of pancreatic malignancy at enrollment, selected as age-matched controls for the PDAC cohort (within ±5 years whenever feasible). Participants will undergo a single 14 mL peripheral blood collection at baseline for comparator translational analyses. No study-specific follow-up is required for control participants.

Eligibility Criteria

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

Study Population

The study population will include adults with newly diagnosed, non-metastatic, treatment-naïve pancreatic ductal adenocarcinoma (PDAC) evaluated at the Pancreatic Surgery Unit of IRCCS Ospedale San Raffaele, and age-matched control patients. Controls will be recruited among patients with intraductal papillary mucinous neoplasm (IPMN) under surveillance at the Pancreatic Cystic Lesion outpatient clinic, with no evidence of pancreatic malignancy at enrollment. Control patients will be selected to match the age of PDAC patients within ±5 years whenever feasible. The study will include 50 PDAC patients and 50 age-matched controls

You may qualify if:

• For all participants:
• Age ≥18 years. Ability and willingness to autonomously provide written informed consent.
• For the PDAC cohort:
• Clinical diagnosis of non-metastatic pancreatic ductal adenocarcinoma (PDAC). Treatment-naïve status at the time of blood collection, with no prior chemotherapy, radiotherapy, or immunotherapy for PDAC.
• Newly diagnosed non-metastatic pancreatic cancer eligible for multimodal treatment.
• Candidate for standard clinical management at IRCCS Ospedale San Raffaele.
• For the age-matched control cohort:
• Patient followed at the Pancreatic Cystic Lesion outpatient clinic of IRCCS Ospedale San Raffaele.
• Diagnosis of intraductal papillary mucinous neoplasm (IPMN) under surveillance, with no evidence of pancreatic malignancy at the time of enrollment.
• Age within ±5 years of the corresponding PDAC cohort to allow age-matched comparator analyses.

You may not qualify if:

• For all participants:
• Inability to autonomously provide informed consent.
• For the PDAC cohort:
• Previous systemic anti-cancer treatment for PDAC. Use of anti-inflammatory drugs, including NSAIDs or immunomodulators. Events or conditions affecting inflammatory parameters, including acute inflammatory or infectious events such as cholangitis, jaundice, or recent invasive procedures.
• Hematologic diseases. Clinically significant hematological abnormalities that may interfere with immune profiling analyses, as assessed by the investigator.
• For the age-matched control cohort:
• Any acute or chronic inflammatory condition or ongoing infection. Any history of cancer or immunological disorders.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood samples (approximately 14 mL per participant), including blood-derived cellular fractions and plasma, collected at baseline for high-dimensional flow cytometry, transcriptomic, epigenetic, protein, and lipid analyses. Samples will be retained only for the time required to complete the planned analyses; any residual biological material will be destroyed after study analyses are completed

MeSH Terms

Conditions

Pancreatic Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Central Study Contacts

Giulio Belfiori

CONTACT

0226437810; belfiori.giulio@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD Surgeon

Study Record Dates

• First Submitted: August 11, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 14, 2026

Record last verified: 2026-08