ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Deferiprone on Oxidative-Stress and Iron-Overload in Low Risk Transfusion-Dependent MDS Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02477631
Recruitment Status : Completed
First Posted : June 23, 2015
Last Update Posted : November 1, 2018
Sponsor:
Collaborators:
Hadassah Medical Organization
Tel Aviv Medical Center
Kaplan Medical Center
Ziv Medical Center
Information provided by (Responsible Party):
Dr. Drorit Merkel, Sheba Medical Center

Brief Summary:

The effect oral iron chelator Deferiprone on the Oxidative stress and on Iron Overload status in transfusion dependent, iron-overloaded low risk MDS patients;

Primary Objective:

• To evaluate the effect of Deferiprone on oxidative stress parameter - Reactive oxygen species (ROS).

Secondary Objectives:

  • To evaluate the effect of Deferiprone on other oxidative stress parameters

    1. Reduced glutathione
    2. Membrane lipid peroxidation
    3. External phosphatidylserine
  • To evaluate the change from baseline to last visit in parameters of iron load.

    1. Serum ferritin (despite ongoing RBC transfusions during the study period).
    2. LIP
    3. LPI
    4. serum hepcidin
  • To evaluate the change from one month preceding baseline visit to last month on study in transfusion requirements.
  • To monitor safety measures:

    1. Adverse events (AEs).
    2. Number of discontinuations due to AEs

Study design:

Single-arm, open-label, multi-center study in 20 iron-overloaded patients with low risk MDS. All participants will be treated with deferiprone for up to 4 months. Patients will have complete blood count monitored weekly, and will visit the site monthly for assessments of safety and efficacy.


Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome With Low-grade Lesions Iron Overload Due to Repeated Red Blood Cell Transfusions Drug: Deferiprone Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Treatment With the Oral Iron Chelator Deferiprone on the Oxidative Stress of Blood Cells and on Iron Overload Status in Transfusion Dependent, Iron-overloaded Patients With Low Risk Myelodysplastic Syndrome
Actual Study Start Date : February 2016
Actual Primary Completion Date : May 2017
Actual Study Completion Date : June 2018


Arm Intervention/treatment
Experimental: Deferiprone
patient treated with study drug
Drug: Deferiprone
This is a single-arm, open-label, multi-center study in 20 patients with MDS. All participants will be treated with deferiprone for up to 4 months.
Other Name: L1, Ferriprox




Primary Outcome Measures :
  1. To evaluate the effect of deferiprone on oxidative stress parameter ROS in iron overloaded and blood dependent patients with MDS. [ Time Frame: 4 months ]
    The change from baseline to end of study in ROS


Secondary Outcome Measures :
  1. To evaluate the effect of Deferiprone on other oxidative stress parameters-Reduced glutathione [ Time Frame: 4 months ]
    The change from baseline to end of study in Reduced glutathione

  2. To evaluate the effect of Deferiprone on other oxidative stress-Membrane lipid peroxidation [ Time Frame: 4 months ]
    The change from baseline to end of study in lipid peroxidation

  3. To evaluate the effect of Deferiprone on other oxidative stress parameters - External phosphatidylserine [ Time Frame: 4 months ]
    The change from baseline to end of study in External phosphatidylserine

  4. To evaluate the change from baseline to last visit in parameters of iron load-serum ferritin levels (despite ongoing RBC transfusions during the study period). [ Time Frame: 4 months ]
    The change from baseline to end of study in serum ferritin levels

  5. To evaluate the change from baseline to last visit in parameters of iron load- LIP [ Time Frame: 4 months ]
    The change from baseline to end of study in serum LIP levels

  6. To evaluate the change from baseline to last visit in parameters of iron load- LPI [ Time Frame: 4 months ]
    The change from baseline to end of study in serum LPI levels

  7. To evaluate the change from baseline to last visit in parameters of iron load- serum hepcidin [ Time Frame: 4 months ]
    The change from baseline to end of study in serum hepcidin levels

  8. To evaluate the change from one month preceding baseline visit to last month on study in transfusion requirements. [ Time Frame: 4 months ]

Other Outcome Measures:
  1. Adverse events (AEs) [ Time Frame: 4 months ]
    Frequency, severity, time to onset, duration, and relatedness to study product and number of discontinuations due to AEs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged ≥ 18 years
  2. Have a documented diagnosis of MDS according to WHO 2008 classification (see appendix I), with an International Prognostic Scoring System (IPSS-R) (see Appendix II) of very low, low or intermediate risk.
  3. Life expectancy of at least 1 year
  4. Serum ferritin level > 1000 ng/mL
  5. Prior receipt of ≥20 RBC units
  6. Females of childbearing potential must have a negative pregnancy test result month prior to start of dosing, In addition, if applicable, they must:

    • Use an effective method of contraception according to local requirements, during the study and within 30 days following their last dose of study medication, OR
    • Have had a tubal ligation (supporting evidence required), OR
    • Have had a hysterectomy (supporting evidence required), OR
    • Participate in a non-heterosexual lifestyle, OR
    • Have a male sexual partner who has been sterilized (supporting evidence required)
  7. Non-sterilized heterosexual males and/or their partners must agree to use an effective method of contraception during the study and for 30 days following their last dose of study medication
  8. All patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and patients must be able to adhere to study restrictions, appointments, and evaluation schedules

Exclusion Criteria:

  1. IPSS-R prognosis of high and very high risk (to avoid the confounding influence of a high blast count)
  2. Unable or unwilling to undergo a 7-day washout period if currently being treated with deferoxamine or deferasirox
  3. Evidence of abnormal liver function (serum ALT level > 5 times upper limit of normal or creatinine level >2 times upper limit of normal)
  4. A serious, unstable illness, as judged by the investigator, during the past 3 months before screening, including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic, or immunologic disease
  5. Myocardial infarction, cardiac arrest, or cardiac failure within 1 year before screening
  6. QT interval prolongation on ECG
  7. Occurrences of severe neutropenia/agranulocytosis (absolute neutrophil count < 0.5 x 109/L
  8. History of allergy or sensitivity to deferiprone or related compounds or to other components of the formulation
  9. Receipt of any investigational products within the past 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication
  10. Participation in any investigational clinical study, other than observational, within the past 30 days; or plans to participate in such a study at any time from the day of enrollment until 30 days post-treatment in the current study
  11. History of drug or alcohol abuse within the last 6 months
  12. Presence of any medical, psychological, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise
  13. Pregnant, breastfeeding, or planning to become pregnant during the study period.
  14. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication
  15. Identified as an investigator or other site staff directly affiliated with this study, or an immediate family member (spouse, parent, child, or sibling, whether biological or legally adopted) of either of the above

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02477631


Locations
Israel
Chim Sheba Medical Center
Tel Hashomer, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
Hadassah Medical Organization
Tel Aviv Medical Center
Kaplan Medical Center
Ziv Medical Center
Investigators
Principal Investigator: Drorit Merkel, MD Sheba Medical Center

Additional Information:
Publications of Results:

Other Publications:
Responsible Party: Dr. Drorit Merkel, Senior physician in the Hematology wing, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02477631     History of Changes
Other Study ID Numbers: SHEBA-15-1908-DM-CTIL
First Posted: June 23, 2015    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018

Keywords provided by Dr. Drorit Merkel, Sheba Medical Center:
Myelodysplastic syndrome
oxidative stress
labile plasma iron

Additional relevant MeSH terms:
Syndrome
Myelodysplastic Syndromes
Preleukemia
Iron Overload
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Iron Metabolism Disorders
Metabolic Diseases
Deferiprone
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action