Myelodysplastic Syndromes
Conditions
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.
Interventions
DRUGDeferasirox (Novartis Pharma)
Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol
Sponsors
Novartis Pharmaceuticals
University of Erlangen-Nürnberg Medical School
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Evaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients | within two years |
| Effectiveness of Iron Depletion | within two years |
| Correlation Between Hematological Improvement and Effectiveness of Iron Depletion | two years |
| Development of Bone Marrow Morphology | 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 |
| Overall Survival | within two years |
| AML-free Survival | within two years |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox Deferasirox (Novartis Pharma): Treatment period 102 weeks. Starting dose 10mg/kg/day. Up to 30/mg/kg according to dose adjustment table as specified in the protocol | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Early termination study | 1 |
Baseline characteristics
| Characteristic | Deferasirox |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 42.5 years |
| Region of Enrollment Germany | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Fraction of Patients With Hematologic Improvement According to Modified IWG Criteria (Reduction of Transfusions and/or Increase in Hb, Improvement of Neutropenia and Thrombocytopenia)
Time frame: within two years
Population: Trial prematurely ended due to insufficient recruitment before Primary endpoint was reached by any subject
Secondary
AML-free Survival
Time frame: within two years
Secondary
Correlation Between Hematological Improvement and Effectiveness of Iron Depletion
Time frame: two years
Secondary
Correlation Between Hematological Improvement and Pretreatment Parameters. Extension of This Analysis to MDS Patients on Deferasirox Within the Licensed Indication (More Severe Iron Overload)
Time frame: two years
Secondary
Development of Bone Marrow Morphology
Time frame: two years
Secondary
Effectiveness of Iron Depletion
Time frame: within two years
Secondary
Evaluate the Safety and Tolerability Profile of Deferasirox in MDS Patients
Time frame: within two years
Secondary
Overall Survival
Time frame: within two years