Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy

NCT06510868 | Recruiting

• 1 other identifier: 22-5247
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective observational study which aims to identify individuals predisposed to developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) could improve patient outcomes in different ways. First, it will enable improved patient selection for PRRT where alternative treatment options are available. Second, understanding the final pathway and how it is modulated by PRRT could allow the design of strategies to halt this process. Third, while it is unknown whether the development of MDS and AML is a late effect of radiopharmaceuticals in general or it is confined to cancer populations or specific radioisotopes will need to be confirmed. Finally, understanding this devastating complication is expected to be the cornerstone towards advancing radiopharmaceuticals' role in the adjuvant setting.

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Identify individuals predisposed to developing MDS/AML to improve patient selection for PRRT where alternative treatment options are available.

  Determining the proportion of patients who screen positive for "prodromal AML genetic panel" pre PRRT.

  5 years

Secondary Outcomes (5)

• Detection of Genetic Mutations in the Blood Post-PRRT

  5 years

• Assessment of Variant Allele Frequencies Post-PRRT

  5 years

• Incidence of Therapy-Related Myeloid Neoplasms (t-MN) Post-PRRT

  5 years

• Proportion of Patients Developing MDS/AML Post-PRRT

  5 years

• Identification of Clonal Mutations Conferring Increased Risk of MDS/AML Post-PRRT

  5 years

Study Arms (3)

Previous PRRT

Patients who have received PRRT within the last 4 years. There are no baseline levels available for cohort A patients. Sample size: 20.

Diagnostic Test: Blood collection

Planned for PRRT

Patients who are scheduled to start PRRT in the next 3 months. Pre-PRRT clonal expansion status will only be available form this cohort. These patients will provide a comprehensive record of development of CH from exposure to PRRT. Sample size: 20.

Radiation: Peptide receptor radionuclide therapy (PRRT); Diagnostic Test: Blood collection

Post PRRT Diagnosed with t-MN (MDS or AML)

Patients who have t-MN (MDS or AML). Sample size: 5.

Diagnostic Test: Blood collection

Interventions

Peptide receptor radionuclide therapy (PRRT) RADIATION

Specialized type of radionuclide therapy used to treat neuroendocrine tumors.

Planned for PRRT

Blood collection DIAGNOSTIC_TEST

Patients will have approximately 5 ml of blood drawn 6,12,24,36,48, 60 months and at the time of MDS/AML diagnosis on follow up. Genomic DNA will be extracted from serum sample using the Qiagen QIAamp DNA Mini Kit. Single-molecule molecular inversion probes (smMIPs) will be used to detect mutations. Single nucleotide variants (SNVs), short insertions and deletions (indels), and mutated myeloid genes will be captured (e.g PPM1D, DNMT3A, TET2, TP53).

Planned for PRRT; Post PRRT Diagnosed with t-MN (MDS or AML); Previous PRRT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This research proposes to study the genetic changes that occur pre-PRRT and post-PRRT using blood samples obtained from a patient population at Princess Margaret Hospital. Cohort A will consist of 20 patients that have had PRRT within the past 4 years. Cohort B will consist of 20 patients planned for PRRT. Cohort C will consist of 1-5 patients post PRRT, diagnosed with t-MN. In other words, patients will already be receiving PRRT or have received PRRT within 4 years.

You may qualify if:

• ECOG 0-3
• Life expectancy \> 6 months
• Informed consent and willingness to undergoing serial genetic panel CHIP testing.
• Cohort Specific criteria
• Cohort A: PRRT completed within 5 years of enrolment
• Cohort B: PRRT planned to commence within 4 months of enrolment
• Cohort C: diagnosis of MDS or AML following prior PRRT.

You may not qualify if:

• Unwillingness to provide blood sample and follow up as per protocol

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples taken for DNA/RNA/Protein analysis with storage on UHN premises. Qiagen QIAamp DNA Mini Kit will be used for extraction.

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Rebecca Wong

CONTACT

416-946-4501; rebecca.wong@uhn.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: July 19, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

CA (1)