AML-MDS Novel Prognostic Tests Clinical Study

Study Overview
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Brief Summary
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This clinical study will provide the study specimens (samples of bone marrow and blood) and the clinical data for a pan-Canadian collaborative research project developed by the MDS/AML Research Consortium. The goal of this project involves the evaluation and potential validation of five novel prognostic tests for myelodysplasia (MDS) and/or acute myeloid leukemia (AML), as well as an analysis of health economic and socio-ethical implications related to the potential introduction of these tests into the clinical setting. The over-arching goal is to improve the outcomes of patients with MDS and AML. The primary hypothesis is that one or more of the laboratory tests being evaluated in conjunction with this study, either alone or in combination with other laboratory tests (either established or under investigation in this project), will have statistically significant prognostic value either alone or in combination with established clinical risk factors. The clinical study will involve the enrollment of 200 adults with AML and 200 adults with MDS over a 2.5 year period. Participants will be followed on study for two years. Bone marrow and blood specimens will be collected at diagnosis and at other time points as required for the development of the five laboratory tests. Participants will be assigned to treatment according to local institutional practice and will be followed for up to 2 years. Health economic and quality of life questionnaires will be administered at key time points. Data will be collected regarding participant characteristics, diagnosis, disease features, treatment and clinical outcome.

Detailed Description
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Two of the tests involve a technology called flow cytometry. Both of the flow cytometry tests are used to predict whether a person is likely to have a good response to chemotherapy or not. Three of the tests involve new genetic-based technology. One of these tests is called comparative genomic profiling. This test can detect genetic abnormalities that current testing methods are not able to detect. Another test involves micro-RNA profiling. The final test involves RNA sequencing. The researchers think these tests might be useful in predicting how well a person will respond to treatment. The novel laboratory tests being evaluated as part of this study are still in the early phases of development and cannot be used for clinical decision making. Participants enrolled in this study will not be informed regarding their individual results with respect to the study tests that are conducted using their biospecimens. The following information (data) will be collected regarding study participants: diagnosis, results of relevant clinical tests, age, gender, treatment and outcome during the 2 year study follow-up period. The study also involves the completion of study questionnaires at six different time points over the course of the two year study follow-up.

Official Title
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A Multi-Centre Observational Prospective Cohort Study Involving the Collection of Clinical Information and Biological Specimens for the Evaluation of Novel Prognostic Tests for Myelodysplasia and Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)

Participation Criteria
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Eligibility Criteria
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There are two parts to the study: Part One (Collection of Biospecimens) and Part Two (Two year follow-up that includes data collection regarding treatment, outcome and questionnaire completion). INCLUSION CRITERIA (PART ONE): Prospective participants can be included in the study if: The participant is 18 years of age or older The participant is suspected to have a new diagnosis of MDS (including CMML) , OR suspected to have a new diagnosis of AML excluding acute promyelocytic leukemia (APL), OR known to have a diagnosis of MDS (including CMML) confirmed by bone marrow aspirate and biopsy no more than one year prior to the date of enrollment AND without commencement of definitive therapy prior to enrollment The participant is scheduled to have a diagnostic or confirmatory bone marrow aspirate and biopsy at a participating site, or in the case of prospective participants with an established diagnosis of MDS (including CMML), must be able to undergo a bone marrow aspirate for the study at the participating site The participant must be able to read and/or understand spoken English or French so that they will be eligible for Part Two of the study The participant must be able to understand and sign the informed consent form applicable to their situation EXCLUSION CRITERIA (PART ONE): Prospective participants should be excluded from the study if: The participant has already received definitive therapy for AML or MDS The participant has a diagnosis of MDS that was confirmed more than one year prior to the date of enrollment INCLUSION CRITERIA (PART TWO): Participants who have been enrolled in Part One will be eligible to participate in the full two year study follow-up component if they meet the following criteria: Confirmed diagnosis of either MDS, CMML or AML (excluding APL) Sufficient cell count for the MDS/AML Clinical Study requirements as follows: For participants with suspected (or known) AML: The blast count of the peripheral blood taken at diagnosis must be greater than 1 x10^6 blast count/mL It must be possible to earmark for the MDS/AML Study: 3 vials 1.0 x 10^7/mL mononuclear peripheral blood cells 1 vial 0.5 x 10^7/mL mononuclear bone marrow cells Cells are to be prepared according to the site's local cell bank procedures so that they can be stored and transported to study labs as needed. At sites participating in the Hogge Assay: In addition to the specimens described above, it must be possible to provide 2 mL of fresh bone marrow or 5 mL of fresh peripheral blood with > 1 x 10^6 blast count/mL For participants with suspected (or known) MDS: It must be possible to earmark for the MDS/AML Study: 2 vials 1.0 x 10^7/mL mononuclear peripheral blood cells 2 vials 1.0 x 10^7/mL mononuclear bone marrow cells Cells are to be prepared according to the site's local cell bank procedures so that they can be stored and transported to study labs as needed. EXCLUSION CRITERIA (PART TWO): Participants who have been enrolled in Part One will not be eligible to participate in the full two year study follow-up component if they: Do not have sufficient cell count for the MDS/AML Clinical Study requirements as set out in Section 11.3 It is confirmed after enrollment that they do not have a diagnosis of MDS, CMML or AML A diagnosis of APL is confirmed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AML Cohort<br>This cohort is comprised of participants who have acute myelogenous leukemia (AML). | |
| MDS Cohort<br>This cohort is comprised of participants who have myelodysplastic syndrome (MDS). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic capacity of the candidate tests (alone and in combination) to predict response to treatment, time to relapse, time to death. | For the AML cohort, the candidate prognostic tests will be analyzed with adjustments for following clinical factors: age, white blood cell count at presentation, antecedent hematologic disorder, FLT-3 status, Karnofsky Performance Status (KPS), cytogenetic sub-group (using WHO 2008). For the MDS cohort the candidate prognostic tests will be analyzed with adjustments for following clinical factors: age, KPS, karyotype, bone marrow blast count and number of cytopenias at diagnosis. | Two years following the completion of enrollment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost impact of candidate tests. | The cost-effectiveness of the candidate tests for AML and MDS treatment will be projected with the aid of economic simulation models. | Two years following the completion of enrollment. | 
| Societal risks and benefits related to the candidate tests. | A comparative analysis of policies and regulations in Canada governing prognostic tests will be undertaken (including tests that utilize RNA and DNA based technologies). In addition, input will be obtained from key stakeholders. This information will be used to develop a set of guidelines and best practices for this type of research. | Two years following the completion of enrollment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, MDS, Economic, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Prognostic