Myelodysplastic Syndrome, Transfusional Iron Overload
Conditions
Keywords
Gastrointestinal adverse events,, myelodysplastic syndrome,, transfusional iron overload diarrhea,, constipation abdominal pain,, vomiting
Brief summary
The objective of the study is to evaluate and compare the frequency and severity of GI adverse events in different dose administration regimens. The patient population consists of low or intermediate (int-1) risk myelodysplastic syndrome (MDS) patients with transfusional iron overload. The study patients are randomized to either a morning dose of 20 mg/kg/day deferasirox or an evening dose of the same. Patients are then followed up for 6 months for any GI events and are assessed using patient reported outcomes tools e.g. a patient diary.
Interventions
DRUGDeferasirox
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent prior to any screening procedures * Male or female patients ≥ 18 years of age * Patient must weigh between 45-135 kg * Patients with low or intermediate (int-1) risk MDS, as determined by IPSS score or RA, RARS by WHO criteria. IPSS must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable Deferasirox naïve: Sexually active pre-menopausal female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation
Exclusion criteria
* History or current GI disease * Systemic diseases which could prevent study treatments * Left ventricular ejection fraction\< 50 % by echo cardiography * Serum creatinine \> 1.2 x ULN at screening * Platelet counts \< 25x 109/L except in cases where guidance is already given in the local deferasirox label * AST or ALT \> 2.5 xULN at screening Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the Frequency of Overall Newly Occurring GI Adverse Events (AEs) in the Two Treatment Arms | 3 months | Study was prematurely terminated and not powered for efficacy. Frequency of GI AEs during the overall study period is available in the AE tables reported in the safety section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Frequency of Specific Commonly Reported GI AEs Between the Two Treatment Groups | months 3 and 6. | Study was prematurely terminated and not powered for efficacy. |
| Difference in Severity of Overall GI AEs Between the Two Treatment Groups | months 3 and 6. | Study was prematurely terminated and not powered for efficacy. |
| Difference in Severity of Specific Commonly Reported GI Symptoms Between the Two Treatment Groups | months 3 and 6 | Study was prematurely terminated and not powered for efficacy. |
| Difference in Frequency of Overall Newly Occurring GI AEs Between the Two Treatment Groups at Month 6. | 6 months | Study was prematurely terminated and not powered for efficacy. |
| the Difference Between the Time From Baseline to the First Occurrence of GI AEs Between the Two Treatment Groups | 3 months, 6 months | Study was prematurely terminated and not powered for efficacy. |
| Difference in Severity of GI Symptoms, Bowel Habits and Level of Satisfaction From the Patient's Perspective Between the Two Treatment Groups | 3 months, 6 months | — |
| Difference in Reducing Serum Ferritin After Each Month of Study Drug Administration Between the Two Groups | 3 months, 6 months | Study was prematurely terminated and not powered for efficacy. |
| Difference in Frequency and Severity of All Non-GI AEs Between the Two Treatment Groups | months 3 and 6 | Study was prematurely terminated and not powered for efficacy. |
Countries
France, Italy, South Africa, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox am Deferasirox 20 mg/kg/day taken in the morning, 30 minutes before food | 7 |
| Deferasirox pm Deferasirox 20 mg/kg/day taken in the evening, no less than 2 hours after the last food intake or at least 30 minutes before the evening meal | 5 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Problems | 5 | 2 |
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Misisng | 1 | 3 |
Baseline characteristics
| Characteristic | Deferasirox am | Deferasirox pm | Total |
|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 7.5 | 71.6 Years STANDARD_DEVIATION 8.65 | 70.5 Years STANDARD_DEVIATION 7.67 |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 2 / 5 |
| serious Total, serious adverse events | 1 / 7 | 2 / 5 |
Outcome results
Primary
Difference in the Frequency of Overall Newly Occurring GI Adverse Events (AEs) in the Two Treatment Arms
Study was prematurely terminated and not powered for efficacy. Frequency of GI AEs during the overall study period is available in the AE tables reported in the safety section.
Time frame: 3 months
Secondary
Difference in Frequency and Severity of All Non-GI AEs Between the Two Treatment Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: months 3 and 6
Secondary
Difference in Frequency of Overall Newly Occurring GI AEs Between the Two Treatment Groups at Month 6.
Study was prematurely terminated and not powered for efficacy.
Time frame: 6 months
Secondary
Difference in Frequency of Specific Commonly Reported GI AEs Between the Two Treatment Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: months 3 and 6.
Secondary
Difference in Reducing Serum Ferritin After Each Month of Study Drug Administration Between the Two Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: 3 months, 6 months
Secondary
Difference in Severity of GI Symptoms, Bowel Habits and Level of Satisfaction From the Patient's Perspective Between the Two Treatment Groups
Time frame: 3 months, 6 months
Secondary
Difference in Severity of Overall GI AEs Between the Two Treatment Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: months 3 and 6.
Secondary
Difference in Severity of Specific Commonly Reported GI Symptoms Between the Two Treatment Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: months 3 and 6
Secondary
the Difference Between the Time From Baseline to the First Occurrence of GI AEs Between the Two Treatment Groups
Study was prematurely terminated and not powered for efficacy.
Time frame: 3 months, 6 months