Sertraline in Treatment of Low-Risk Myelodysplastic Syndrome (SS1)

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Sertraline; Procedure: Bone Marrow Aspirate/Biopsy

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gustavo Rivero
• Collaborators: Baylor College of Medicine
• Investigators: Principal Investigator: Gustavo A Rivero, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Anemia; Leukemia; Preleukemia; Bone marrow diseases; Cytopenias; Hematologic diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: H-36160