Early treatment with deferasirox (Exjade®) in low risk MDS - Exjade-Early-Trial

• Conditions: Patients presenting with low or INT-1 risk MDS with only mild iron overload will be treated with deferasirox in this study. It will be analyzed if hematological improvement can be observed during this treatment.

• Registration Number: EUCTR2008-006268-12-DE
• Lead Sponsor: Friedrich-Alexander-Universitaet Erlangen-Nuernberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-20
• Last Update Posted: 3 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

-MDS of subtype RA, RARS, RCMD, RCMD-RS (i.e. lower risk)
-RAEB I allowed, if clinically stable for > 3 months
-5q-minus syndrome allowed, if lenalidomide unsuccessful or unavailable at the time
of inclusion
-IPSS score < intermediate-1
-transfusion dependent or Hb < 10,5 g/dl
-History of less than 20 units of red blood cell transfusions or 100mL/kg of
prepacked red blood cells (PRBCs), except for tranfusions for acute bleeding
-Serum ferritin > 300 µg/l and < 1500 µg/l. This level should have been verified at
least at two occasions within 3 months. Samples must be obtained in the absence
of concomitant severe infection
-no indication for EPO (due to high endogenous EPO levels) or EPO without benefit
in the past
-no indication and/or no plans for cytostatic drugs
-no previous exposure to cytostatic drugs, thalidomide, lenalidomide, G-CSF or EPO
or exposure to any of these drugs has been terminated since > 8 weeks (4 weeks
for G-CSF).
-no indication and/or no plans for stem cell transplantation
-stable or worsening cytopenia during the past 8 weeks. If in doubt, extend
screening period to > 8 weeks
-Patients of either gender and age > 18 years
-Life expectancy > 12 months
-Females of childbearing potential must use double-barrier contraception.
-Written informed consent by the patient

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Treatment with deferasirox or other chelation therapy for periods > 4 weeks before
study start
-Patients with a concomitant second malignant disease, possibly interfering with life
expectancy
-Patients with mean levels of alanine aminotransferase (ALT) > 5x ULN
-Patients with uncontrolled systemic hypertension
-Patients with serum creatinine > 1.5x the upper limit of normal (ULN) or a creatinine
clearance < 60 ml/min according to the MDRD formula (Levey 2005)
-History of nephrotic syndrome
-Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
-Patients with psychiatric or addictive disorders which prevent them from giving their
informed consent or undergoing study treatment
-Patients treated with systemic investigational drugs within the past 4 weeks or
topical investigational drug within the past 7 days
-Any other surgical or medical condition which might significantly alter the
absorption, distribution, metabolism or excretion of any drug. The investigator
should be guided by evidence of any of the following:
*history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or
rectal bleeding;
*history of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection;
*history of pancreatic injury or pancreatitis; indications of impaired pancreatic
function/injury as indicated by abnormal lipase or amylase;
*history of urinary obstruction or difficulty in voiding
-History of non-compliance to medical regimens and patients who are considered
potentially unreliable and/or not cooperative
-History of drug or alcohol abuse within the 12 months prior to dosing or evidence of
such abuse as indicated by the laboratory assays conducted during the run-in period
-Patients with active uncontrolled infectious disease
-Pregnancy or breast feeding
-QT > 470 msec on screening ECG
-Patients with a history of Torsades de Pointes

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Fraction of patients with hematologic improvement according to modified IWG criteria (reduction of transfusions and/or increase in Hb, improvement of neutropenia and thrombocytopenia);Secondary Objective: - Evaluate the safety and tolerability profile of deferasirox in MDS patients <br>-Effectiveness of iron depletion <br>-Correlation between hematological improvement and effectiveness of iron depletion <br>-Development of bone marrow morphology<br>-Correlation between hematological improvement and pretreatment parameters. <br> Extension of this analysis to MDS patients on deferasirox within the licensed <br> indication (more severe iron overload)<br>-overall survival<br>-AML-free survival<br>;Primary end point(s): Fraction of patients with hematologic improvement according to modified IWG criteria (reduction of transfusions and/or increase in Hb, improvement of neutropenia and thrombocytopenia)