Sertraline in Treatment of Low-Risk Myelodysplastic Syndrome

Study Overview
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Brief Summary
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This study will investigate the effects of sertraline in people with low-risk myelodysplastic syndrome (MDS). It is hoped that sertraline will decrease disease progression and reduce the need for blood transfusions.

Detailed Description
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This pilot study investigates clinical benefit of four 28-day cycles of sertraline in low-risk MDS patients. Participants will receive 100mg of oral sertraline daily. The study will also evaluate potential associated biological mechanisms of action.

Official Title
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SS1: Pilot Study of Sertraline in Treatment of Low-Risk Myelodysplastic Syndrome (MDS)

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Sertraline
* Procedure: Bone Marrow Aspirate/Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Very Low or Low risk MDS defined by IPSS-R confirmed by a bone marrow aspirate and biopsy (Blast count must be < 20%) Hemoglobin < 11 g/dL, or transfusion dependency. Platelet count <100,000/mm3 Absolute Neutrophil Count (ANC) < 1000/mm3 Life expectancy of 12 months or greater ECOG Performance status of 0 - 3 Age ≥ 18 years Willing to use medically acceptable methods of birth control during the study and for 28 days after discontinuing study treatment All subjects must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines Both men and women and members of all races and ethnic groups Exclusion Criteria: Previous exposure to 5-AC (azacitidine) or decitabine Use of antidepressants such as sertraline within 6 weeks OR use of paroxetine, fluoxetine, or citalopram within 3 months prior to registration Active cases (within past 12 months) of depressive disorder, manic episodes, and/or anxiety requiring active treatment with an SSRI. Patients being treated with an SSRI for non-psychiatric indication are allowed, and should go through the appropriate washout. Previous or concurrent malignancy, except treated basal cell or squamous cell cancer of skin, treated in situ cervical cancer, treated lobular or ductal carcinoma in situ in one breast, or any other cancer for which the patient has been disease-free for at least 5 years Actively receiving chemo-immunotherapy Evidence of active infection Treatment with steroids or immunosuppressive therapy such as cyclosporine, tacrolimus, anti-thymocyte globulin (ATG) within 6 months of registration Platelet transfusion within 8 weeks of registration. Platelet count < 20,000/mm3 within 14 days of registration. Active treatment with growth factors such erythropoietin stimulating agent (ESA), granulocyte colony-stimulating factor (GCSF), thrombopoietin stimulating factor within 8 weeks of registration Treatment with an investigational agent within 4 weeks of registration History of autoimmune disease including rheumatoid arthritis, systemic lupus and sarcoidosis History of allergic reactions attributed to compounds of similar chemical or biologic composition to sertraline Known history of splenomegaly Pregnant or nursing women are excluded from this study because Sertraline is a Class C agent with the potential for teratogenic or abortive effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sertraline, breast feeding should be discontinued. HIV: Given high risk for Immune thrombocytopenic purpura, HIV associated neutropenia and combination antiretroviral therapy, patients with known HIV are excluded because of the potential for pharmacokinetic interactions with sertraline. Any condition or illness that, in the Investigator's opinion, would place the subject at unacceptable risk if he/she were to participate.

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertraline<br>Sertraline tablets 100mg daily for 4 (28-day) cycles | Drug: Sertraline<br> <br> * Other names: Zoloft;Procedure: Bone Marrow Aspirate/Biopsy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological Improvement - minor (HI-minor) | Improvement in erythroid, neutrophil or platelet | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI-minor response rate | HI-minor response rate Cycle 1 | 4 weeks | 
| HI-minor response rate | HI-minor response rate Cycle 2 | 8 weeks | 
| HI-minor response rate | HI-minor response rate Cycle 3 | 12 weeks | 
| HI-minor response rate | HI-minor response rate Cycle 4 | 16 weeks | 
| Individual rates of HI minor measurements: erythroid, neutrophil and platelet | Individual rates of HI minor measurements at Cycle 1: erythroid, neutrophil and platelet | 4 weeks | 
| Individual rates of HI minor measurements: erythroid, neutrophil and platelet | Individual rates of HI minor measurements at Cycle 2: erythroid, neutrophil and platelet | 8 weeks | 
| Individual rates of HI minor measurements: erythroid, neutrophil and platelet | Individual rates of HI minor measurements at Cycle 3: erythroid, neutrophil and platelet | 12 weeks | 
| Individual rates of HI minor measurements: erythroid, neutrophil and platelet | Individual rates of HI minor measurements at Cycle 4: erythroid, neutrophil and platelet | 16 weeks | 
| Hematological Improvement - major (HI-major) response rate | HI-major response rate at Cycle 1 | 4 weeks | 
| Hematological Improvement - major (HI-major) response rate | HI-major response rate at Cycle 2 | 8 weeks | 
| Hematological Improvement - major (HI-major) response rate | HI-major response rate at Cycle 3 | 12 weeks | 
| Hematological Improvement - major (HI-major) response rate | HI-major response rate at Cycle 4 | 16 weeks | 
| Individual rates of HI major measurements: erythroid, neutrophil and platelet | Individual rates of HI major measurements at Cycle 1: erythroid, neutrophil and platelet | 4 weeks | 
| Individual rates of HI major measurements: erythroid, neutrophil and platelet | Individual rates of HI major measurements at Cycle 2: erythroid, neutrophil and platelet | 8 weeks | 
| Individual rates of HI major measurements: erythroid, neutrophil and platelet | Individual rates of HI major measurements at Cycle 3: erythroid, neutrophil and platelet | 12 weeks | 
| Individual rates of HI major measurements: erythroid, neutrophil and platelet | Individual rates of HI major measurements at Cycle 4: erythroid, neutrophil and platelet | 16 weeks | 
| Serum cytokine level modifications | Measured as the difference between Week 4 and pre-treatment levels | 4 weeks | 
| Serum cytokine level modifications | Measured as the difference between Week 8 and pre-treatment levels | 8 weeks | 
| Serum cytokine level modifications | Measured as the difference between Week 12 and pre-treatment levels | 12 weeks | 
| Serum cytokine level modifications | Measured as the difference between Week 16 and pre-treatment levels | 16 weeks | 
| Changes in the Gene Expression Profile | Measured as the difference between Day 14 and Baseline | Between Baseline and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Leukemia, Hematologic diseases, Cytopenias, Bone marrow diseases, Preleukemia