Exjade-Early-Trial

Condition(s) targeted: Myelodysplastic Syndromes

Intervention: Deferasirox (Novartis Pharma) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Erlangen-Nürnberg Medical School

Official(s) and/or principal investigator(s):
Stefan Krause, Prof. Dr., Study Chair, Affiliation: Medizinische Klinik 5, Universitätsklinikum Erlangen

Overall contact:
Stefan Krause, Prof. Dr., Phone: +49 9131 85, Ext: 35957

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.

Official title: Early Treatment With Deferasirox (Exjade®) in Low Risk MDS - a Prospective Multicentre Single-arm Single-stage Phase II Study -

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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 outcome:

Evaluate the safety and tolerability profile of deferasirox in MDS patients

Effectiveness of iron depletion

Correlation between hematological improvement and effectiveness of iron depletion

Development of bone marrow morphology

Correlation between hematological improvement and pretreatment parameters. Extension of this analysis to MDS patients on deferasirox within the licensed indication (more severe iron overload)

overall survival

AML-free survival

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Stefan Krause, Prof. Dr., Phone: +49 9131 85, Ext: 35957

Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Bavaria 91054, Germany; Recruiting
Stefan Krause, Prof. Dr., Phone: +49 9131 85, Ext: 35957
Stefan Krause, Prof. Dr., Principal Investigator

Starting date: April 2010
Last updated: June 11, 2010