Ignite Creation Date:
2025-12-24 @ 5:55 PM
Ignite Modification Date:
2026-02-22 @ 5:08 PM
Study NCT ID:
NCT06510868
Status:
RECRUITING
Last Update Posted:
2025-02-10
First Post:
2024-07-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009190', 'term': 'Myelodysplastic Syndromes'}, {'id': 'D015470', 'term': 'Leukemia, Myeloid, Acute'}], 'ancestors': [{'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007951', 'term': 'Leukemia, Myeloid'}, {'id': 'D007938', 'term': 'Leukemia'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples taken for DNA/RNA/Protein analysis with storage on UHN premises. Qiagen QIAamp DNA Mini Kit will be used for extraction.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 45}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-08-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-02', 'completionDateStruct': {'date': '2029-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-02-06', 'studyFirstSubmitDate': '2024-07-12', 'studyFirstSubmitQcDate': '2024-07-18', 'lastUpdatePostDateStruct': {'date': '2025-02-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-07-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-04-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Identify individuals predisposed to developing MDS/AML to improve patient selection for PRRT where alternative treatment options are available.', 'timeFrame': '5 years', 'description': 'Determining the proportion of patients who screen positive for "prodromal AML genetic panel" pre PRRT.'}], 'secondaryOutcomes': [{'measure': 'Detection of Genetic Mutations in the Blood Post-PRRT', 'timeFrame': '5 years', 'description': 'Enrolled patients will undergo serial genetic panel testing of blood samples annually for up to 5 years to detect genetic mutations.'}, {'measure': 'Assessment of Variant Allele Frequencies Post-PRRT', 'timeFrame': '5 years', 'description': '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.'}, {'measure': 'Incidence of Therapy-Related Myeloid Neoplasms (t-MN) Post-PRRT', 'timeFrame': '5 years', 'description': '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.'}, {'measure': 'Proportion of Patients Developing MDS/AML Post-PRRT', 'timeFrame': '5 years', 'description': '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.'}, {'measure': 'Identification of Clonal Mutations Conferring Increased Risk of MDS/AML Post-PRRT', 'timeFrame': '5 years', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Myelodysplastic Syndrome', 'Acute Myeloid Leukemia']}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': '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.\n\nWhile 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.\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ECOG 0-3\n* Life expectancy \\> 6 months\n* Informed consent and willingness to undergoing serial genetic panel CHIP testing.\n* Cohort Specific criteria\n\n 1. Cohort A: PRRT completed within 5 years of enrolment\n 2. Cohort B: PRRT planned to commence within 4 months of enrolment\n 3. Cohort C: diagnosis of MDS or AML following prior PRRT.\n\n Exclusion Criteria:\n* Unwillingness to provide blood sample and follow up as per protocol'}, 'identificationModule': {'nctId': 'NCT06510868', 'acronym': 'MDS & PRRT', 'briefTitle': 'Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy', 'organization': {'class': 'OTHER', 'fullName': 'University Health Network, Toronto'}, 'officialTitle': 'Evaluating Myelodysplastic Syndrome Risks in NET Patients Planned for Peptide Radionuclide Therapy', 'orgStudyIdInfo': {'id': '22-5247'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Previous PRRT', 'description': 'Patients who have received PRRT within the last 4 years. There are no baseline levels available for cohort A patients. Sample size: 20.', 'interventionNames': ['Diagnostic Test: Blood collection']}, {'label': 'Planned for PRRT', 'description': '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.', 'interventionNames': ['Radiation: Peptide receptor radionuclide therapy (PRRT)', 'Diagnostic Test: Blood collection']}, {'label': 'Post PRRT Diagnosed with t-MN (MDS or AML)', 'description': 'Patients who have t-MN (MDS or AML). Sample size: 5.', 'interventionNames': ['Diagnostic Test: Blood collection']}], 'interventions': [{'name': 'Peptide receptor radionuclide therapy (PRRT)', 'type': 'RADIATION', 'description': 'Specialized type of radionuclide therapy used to treat neuroendocrine tumors.', 'armGroupLabels': ['Planned for PRRT']}, {'name': 'Blood collection', 'type': 'DIAGNOSTIC_TEST', 'description': '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).', 'armGroupLabels': ['Planned for PRRT', 'Post PRRT Diagnosed with t-MN (MDS or AML)', 'Previous PRRT']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Rebecca Wong, MD', 'role': 'CONTACT', 'email': 'rebecca.wong@rmp.uhn.on.ca', 'phone': '416-946-4501', 'phoneExt': '5736'}], 'facility': 'Princess Margaret Cancer Centre', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'centralContacts': [{'name': 'Rebecca Wong', 'role': 'CONTACT', 'email': 'rebecca.wong@uhn.ca', 'phone': '416-946-4501', 'phoneExt': '5736'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Health Network, Toronto', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}