Sertraline in Treatment of Low-Risk Myelodysplastic Syndrome

Phase 1

Terminated

• Conditions: Myelodysplastic Syndromes
• Interventions: Drug: Sertraline; Procedure: Bone Marrow Aspirate/Biopsy

• Registration Number: NCT02452983
• Lead Sponsor: Gustavo Rivero

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-05
• Study First Submitted: 2015-05-21
• Study First Submitted QC: 2015-05-22
• Study First Posted: 2015-05-25
• Primary Completion: 2020-11
• Study Completion: 2020-11
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-31
• Last Update Posted: 2022-06-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sertraline	Sertraline	Sertraline tablets 100mg daily for 4 (28-day) cycles
Sertraline	Bone Marrow Aspirate/Biopsy	Sertraline tablets 100mg daily for 4 (28-day) cycles

Primary Outcome Measures

Name	Time	Method
Hematological Improvement - minor (HI-minor)	16 weeks	Improvement in erythroid, neutrophil or platelet

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Michael E. DeBakey VA Medical Center; 🇺🇸 Houston, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States