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NCT Number: NCT06510868

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

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.

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Key information

Conditions

Myelodysplastic Syndrome Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms Neoplasms by Histologic Type

Sex eligibility

All sexes

Study type

Observational

Primary location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location status: Recruiting

Location contact

Rebecca Wong, MD

CONTACT

[email protected]

416-946-4501 ext. 5736

About this study

Radiopharmaceuticals is currently used for the treatment of metastatic cancer date. While radiopharmaceuticals are generally well tolerated, one of its most devastating long-term toxicities is the development of therapy related myeloid neoplasms (t-MN), an umbrella term for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). PRRT (Receptor Radionuclide Therapy) is a targeted radiopharmaceutical therapy (RPT) used to treat neuroendocrine tumors. RPTs use drugs to attack cancer cells while reducing harm to healthy tissue. PRRT delivers high doses of radiation to tumors in the body to destroy or slow their growth and reduce disease side effects.

While PRRT is generally well tolerated, one of its long-term side effects is the development of therapy related myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The identification of genetic changes that lead to the development of MDS and AML during PRRT is a growing area of research. It is now known that the genetic changes that lead to progression into AML typically occur through many years of pre-leukemic hematopoietic stem cell clonal evolution, before development of late mutations that lead to malignant disease. The short interval between exposure to PRRT and appearance of MDS and AML would suggest some patients are already at high risk of developing AML and are potentially detectable. The ability to identify individuals predisposed to developing MDS/AML could improve patient selection for PRRT and design strategies to mitigate the development of MDS/AML.

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

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

Treatment and study plan

Peptide receptor radionuclide therapy (PRRT)

Radiation

Specialized type of radionuclide therapy used to treat neuroendocrine tumors.

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).

Primary outcomes

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

    Time frame: 5 years

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

Secondary outcomes

  1. Detection of Genetic Mutations in the Blood Post-PRRT

    Time frame: 5 years

    Enrolled patients will undergo serial genetic panel testing of blood samples annually for up to 5 years to detect genetic mutations.

  2. Assessment of Variant Allele Frequencies Post-PRRT

    Time frame: 5 years

    Annual genetic panel testing will be conducted to determine variant allele frequencies in the blood of patients post-PRRT for up to 5 years. The frequencies of specific gene mutations (e.g., PPM1D, TET2, DNMT3A, TP53) will be measured and analyzed in relation to clinical characteristics and treatment history.

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

    Time frame: 5 years

    The incidence of therapy-related myeloid neoplasms (MDS and AML) will be monitored in patients post-PRRT over a 5-year follow-up period. Data will include the time to t-MN development and any associated genetic mutations identified through annual blood genetic testing.

  4. Proportion of Patients Developing MDS/AML Post-PRRT

    Time frame: 5 years

    Enrolled patients will undergo annual genetic panel testing for up to 5 years to determine the proportion who develop myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) after receiving PRRT. Data collected will include baseline clinical characteristics, the amount of PRRT received, prior antineoplastic therapies, and PRRT-related adverse events to help identify factors associated with the development of these conditions.

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

    Time frame: 5 years

    Enrolled patients will undergo annual genetic panel testing for up to 5 years to identify clonal mutations associated with an increased risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) after receiving PRRT.

Study contacts

Contact information is provided by the study sponsor or research team.

Rebecca Wong

CONTACT

[email protected]

416-946-4501 ext. 5736

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Registry information

Acronym: MDS & PRRT

Important dates

Study start
2024
Primary completion
2028
Study completion
2029
First posted
Jul 19, 2024
Registry last updated
Mar 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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