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

• Status: Completed
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheba Medical Center
• Collaborators: Hadassah Medical Organization; Kaplan Medical Center; Tel Aviv Medical Center; Ziv Medical Center
• Treatments: Deferiprone

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