Clinical trial NCT06510868: Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy
Official title: Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myelodysplastic Syndrome
Acute Myeloid Leukemia
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2024-07-19
Enrollment: 45
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* ECOG 0-3
* Life expectancy \> 6 months
* Informed consent and willingness to undergoing serial genetic panel CHIP testing.
* Cohort Specific criteria

  1. Cohort A: PRRT completed within 5 years of enrolment
  2. Cohort B: PRRT planned to commence within 4 months of enrolment
  3. Cohort C: diagnosis of MDS or AML following prior PRRT.

     Exclusion Criteria:
* Unwillingness to provide blood sample and follow up as per protocol

Primary outcomes:
measure: Identify individuals predisposed to developing MDS/AML to improve patient selection for PRRT where alternative treatment options are available.
timeFrame: 5 years
Secondary outcomes:
measure: Detection of Genetic Mutations in the Blood Post-PRRT
timeFrame: 5 years
measure: Assessment of Variant Allele Frequencies Post-PRRT
timeFrame: 5 years
measure: Incidence of Therapy-Related Myeloid Neoplasms (t-MN) Post-PRRT
timeFrame: 5 years
measure: Proportion of Patients Developing MDS/AML Post-PRRT
timeFrame: 5 years
measure: Identification of Clonal Mutations Conferring Increased Risk of MDS/AML Post-PRRT
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
References: