Exjade-Early-Trial

Phase 2

Terminated

Conditions: Myelodysplastic Syndromes

Interventions: Drug: Deferasirox (Novartis Pharma)

Registration Number: NCT01058369

Lead Sponsor: University of Erlangen-Nürnberg Medical School

Brief Summary: Study outline: Deferasirox (Exjade®) is regularly used in severe iron overload in order to avoid organ damage of liver, heart and other organs. It has been proposed, that iron overload may not only impose damage to other organs but also to the bone marrow and thus worsen hematopoietic insufficiency in patients with MDS. 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

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 transfusions 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 (for example orale contraception and condom).
Mental ability of the patient to understand explications concerning the study and to understand and follow instructions of the investigating physician
Written informed consent by the patient

Exclusion Criteria

Treatment with deferasirox or other chelation therapy for periods > 4 weeks before study start
Patients with intolerance to Deferasirox
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 laboratory assays conducted during the screening 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

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Deferasirox	Deferasirox (Novartis Pharma)	-

Primary Outcome Measures

Name	Time	Method
Fraction of Patients With Hematologic Improvement According to Modified IWG Criteria (Reduction of Transfusions and/or Increase in Hb, Improvement of Neutropenia and Thrombocytopenia)	within two years

Secondary Outcome Measures

Name	Time	Method
Evaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients	within two years
Development of Bone Marrow Morphology	two years
Effectiveness of Iron Depletion	within two years
Overall Survival	within two years
Correlation Between Hematological Improvement and Effectiveness of Iron Depletion	two years
Correlation Between Hematological Improvement and Pretreatment Parameters. Extension of This Analysis to MDS Patients on Deferasirox Within the Licensed Indication (More Severe Iron Overload)	two years
AML-free Survival	within two years