Low and Int 1-risk Myelodysplastic Syndrome
Conditions
Keywords
myelodysplastic syndrome, MDS, myelodysplasia, blood disorder, cytopenias, low blood counts, progressive bone marrow failure, adult, ICL570, deferasirox, erythropoietin, erythropoiesis, NF-kB pathway, hematopoiesis.
Brief summary
The primary purpose of this trial was is to assess the effect of treatment with deferasirox combined with erythropoietin vs. erythropoietin alone on erythropoiesis in patients with low- and int-1-risk myelodysplastic syndrome. The addition of deferasirox to erythropoietin can lead to a potential synergism with the reduction of reactive oxygen species, through both the NF-kB pathway and the control of free toxic iron. This may create a better environment in the bone marrow for a better response with erythropoietin. This study was designed to test in a prospective way the combination of deferasirox with erythropoietin in terms of their effect on hematopoiesis.
Detailed description
This study did not meet the original enrollment objective of 60 patients and was terminated without extending enrollment past original planned LPFV of 31-Oct-2016.
Interventions
DRUGDeferasirox DFX, DT
provided as dispersible tablets for oral use in 125 and 250, 500 mg
DRUGDeferasirox DFX, FCT
provided as film-coated tablet for oral use in 90, 180, 360 mg strengths
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients who had low- and Int-1-risk myelodysplastic syndrome * Documented diagnosis of the following: Myelodysplastic syndrome that lasted ≥ 3 months and \< 3 years Disease must not have been secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases * A hemoglobin \< 10 g/dL and ≥ 8 g/dL * History of transfusions \< 10 RBC units and must not have been RBC transfusion dependent * 300 ng/mL \< serum ferritin \< 1,500 ng/mL (Values within 10% difference above 1500 ng/ml or 10% difference below 300 ng/ml could have been accepted at the investigator's discretion. * Endogenous erythropoietin levels \< 500 units/L * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) * Creatinine clearance above the concentration limit in locally approved prescribing information (PI). Patients with creatinine clearance between 40 and less than 60 mL/min, who did not present with additional risk factors that might impair renal function, were eligible at the discretion of the investigator Key
Exclusion criteria
* Patients who had MDS with isolated del(5q) * Patients who had received prior EPO treatment or other recombinant growth factors regardless of the outcome (Patient who had received prior EPO treatment or other recombinant growth factors for less than 4 weeks and not within 3 months before screening without a documented response are allowed) * Patients who had received steroids or immunosuppressive therapy for the improvement of hematological parameters (stable steroid treatment for adrenal failure or chronic medical conditions, and intermittent dexamethasone as antiemetics were allowed). * B12 and folate deficient patients with and without clinical symptoms (patients were rescreened after successful therapy of B12 and folate deficiency) * Uncontrolled seizures or uncontrolled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) | Baseline up to 12 weeks | Difference in percentage of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria increase in hemoglobin (Hb) ≥ 1.5 g/dL. Erythroid response is defined as the increase in Hb from baseline ≥ 1.5 g/dL. Patients achieving erythroid response at least once within 12 weeks were considered responders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Baseline up to 24 weeks | Percentage of participants achieving an hematologic improvement defined as: neutrophil improvement: increase from baseline \>0.5 × 10\^9/L (baseline = 1.0 × 10\^9/L ), platelet improvement: increase from baseline ≥ 30 × 10\^9/L (baseline = 100 × 10\^9/L), hemoglobin improvement: Hb increase from baseline ≥ 1 g/dL (baseline\<11 g/dL) |
| Absolute Change in Hemoglobin Values up to 24 Weeks | Baseline up to 24 weeks | Absolute change in hemoglobin values for patients showing improvement: Hemoglobin improvement Hb increase from baseline ≥ 1 g/dL (baseline\<11 g/dL) |
| Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks | Baseline up to 24 weeks | Absolute change in platelets and neutrophil levels for participants showing improvement: neutrophil improvement: increase from baseline \>0.5 × 10\^9/L (baseline = 1.0 × 10\^9/L ), platelet improvement: increase from baseline ≥ 30 × 10\^9/L (baseline = 100 × 10\^9/L) |
| Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) | Week 13 up to 24 weeks | Erythroid response: hemoglobin increase from baseline \> = 1.5 g/dL (baseline \<11 g/dL) |
| Summary of Erythroid Response Within 24 Weeks in Participants Randomized to EPO at Baseline and Not Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) | baseline up to 24 weeks | Erythroid response: hemoglobin increase from baseline \> = 1.5 g/dL (baseline \<11 g/dL). Percentages are based on N. Confidence intervals are calculated using Clopper-Pearson method. Hemoglobin value is at time of first response |
| Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set) | Baseline up to 24 weeks | Hematological response criteria defined as: Erythroid response: hemoglobin (Hb) increase from baseline \>= 1.5 g/dL (baseline \< 11 g/dL), neutrophil response: increase from baseline \>= 100% and increase \> 0.5 × 10\^9/L (baseline \<1 × 10\^9/L), platelet response: increase from baseline \>= 30 × 10\^9/L (baseline \<100 × 10\^9/L) according to modified IWG 2006 criteria |
| Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Baseline up to 24 weeks | Absolute change in serum ferritin from baseline |
| Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Baseline up 24 weeks | Absolute change in serum ferritin from baseline |
| Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Baseline up to 24 weeks | This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. |
| Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Baseline up to 24 weeks | This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. |
| Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Baseline up to 24 weeks | This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. The time-course of Hb and its absolute changes from baseline was summarized by descriptive statistics by visit and erythroid response. Patients randomized to EPO and not switching after 12 weeks to EPO+DFX would consist of only responders. |
| Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Baseline up to 24 weeks | Absolute change in serum ferritin from baseline |
Countries
Algeria, Argentina, Canada, China, Germany, Italy, South Korea, Spain, Sweden, United Kingdom
Participant flow
Pre-assignment details
Twenty-three patients were randomized into the trial
Participants by arm
| Arm | Count |
|---|---|
| Erythropoietin Alpha Starting dose was erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were switched to the combination arm. At any time when erythroid response was achieved, erythropoietin treatment was stopped until end of study. | 12 |
| Deferasirox + Erythropoietin Alpha Starting dose was deferasirox dispersible tablet (DT) 10 mg/kg/day or deferasirox film-coated tablet FCT) 7 mg/kg/day in combination with erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement was inadequate, erythropoietin dose was escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement was inadequate, participants were discontinued from the study. At any time when erythroid response was achieved, erythropoietin treatment was stopped study and Deferasirox treatment was continued until end of study | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Disease progression | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Erythropoietin Alpha | Deferasirox + Erythropoietin Alpha | Total |
|---|---|---|---|
| Age, Continuous | 74.5 years STANDARD_DEVIATION 5.84 | 71.1 years STANDARD_DEVIATION 7.54 | 72.9 years STANDARD_DEVIATION 6.77 |
| Race/Ethnicity, Customized Asian | 4 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized Caucasian | 8 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 10 | 0 / 1 | 0 / 5 |
| other Total, other adverse events | 4 / 7 | 10 / 10 | 1 / 1 | 5 / 5 |
| serious Total, serious adverse events | 1 / 7 | 1 / 10 | 1 / 1 | 1 / 5 |
Outcome results
Primary
Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set)
Difference in percentage of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria increase in hemoglobin (Hb) ≥ 1.5 g/dL. Erythroid response is defined as the increase in Hb from baseline ≥ 1.5 g/dL. Patients achieving erythroid response at least once within 12 weeks were considered responders
Time frame: Baseline up to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erythropoietin Alpha | Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) | 41.7 percentage of participants |
| Deferasirox + Erythropoietin Alpha | Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) | 27.3 percentage of participants |
95% CI: [-24, 48.16]
Secondary
Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set)
Hematological response criteria defined as: Erythroid response: hemoglobin (Hb) increase from baseline \>= 1.5 g/dL (baseline \< 11 g/dL), neutrophil response: increase from baseline \>= 100% and increase \> 0.5 × 10\^9/L (baseline \<1 × 10\^9/L), platelet response: increase from baseline \>= 30 × 10\^9/L (baseline \<100 × 10\^9/L) according to modified IWG 2006 criteria
Time frame: Baseline up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set) | 1.8 g/dL | Standard Deviation 0.21 |
| Deferasirox + Erythropoietin Alpha | Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set) | 2.1 g/dL | Standard Deviation 0.61 |
Secondary
Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.
Time frame: Baseline up to 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 5 | 0.7 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 9 | 1.6 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 13 | 2.9 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 17 | 2.4 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 21 | 1.7 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 5 | -0.1 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 13 | 0.2 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 17 | -0.5 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 21 | -0.6 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 9 | 0.0 g/dL |
Secondary
Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy. The time-course of Hb and its absolute changes from baseline was summarized by descriptive statistics by visit and erythroid response. Patients randomized to EPO and not switching after 12 weeks to EPO+DFX would consist of only responders.
Time frame: Baseline up to 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 5 | 1.2 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 9| | 1.8 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 13| | 0.7 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 17| | -0.6 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 5 | 0.3 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 9| | 0.5 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 13 | 0.4 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 17| | 0.0 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 21 | 0.0 g/dL |
Secondary
Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set)
This analysis included patients randomized either to EPO or DFX+EPO at baseline as well as patients who did not have erythroid response at week 12 in the EPO group and switched to combination therapy.
Time frame: Baseline up to 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 5 | 1.5 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 9 | 1.9 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 13 | 1.7 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 17 | 1.6 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 21 | 0.8 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 5 | -0.9 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 9 | -1.7 g/dL |
| Erythropoietin Alpha | Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 13 | -2.5 g/dL |
Secondary
Absolute Change in Hemoglobin Values up to 24 Weeks
Absolute change in hemoglobin values for patients showing improvement: Hemoglobin improvement Hb increase from baseline ≥ 1 g/dL (baseline\<11 g/dL)
Time frame: Baseline up to 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Hemoglobin Values up to 24 Weeks | 1.3 g/dL | Standard Deviation 0.37 |
| Deferasirox + Erythropoietin Alpha | Absolute Change in Hemoglobin Values up to 24 Weeks | 1.4 g/dL | Standard Deviation 0.55 |
Secondary
Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks
Absolute change in platelets and neutrophil levels for participants showing improvement: neutrophil improvement: increase from baseline \>0.5 × 10\^9/L (baseline = 1.0 × 10\^9/L ), platelet improvement: increase from baseline ≥ 30 × 10\^9/L (baseline = 100 × 10\^9/L)
Time frame: Baseline up to 24 weeks
Population: Number of patients who met criteria varied across parameters
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks | Platelets | 58.7 10^9 cells/L | Standard Deviation 23.93 |
| Erythropoietin Alpha | Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks | Neutrophils | 1.2 10^9 cells/L | Standard Deviation 1.16 |
| Deferasirox + Erythropoietin Alpha | Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks | Platelets | 66.3 10^9 cells/L | Standard Deviation 22.74 |
| Deferasirox + Erythropoietin Alpha | Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks | Neutrophils | 2.4 10^9 cells/L | Standard Deviation 1.57 |
Secondary
Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
Absolute change in serum ferritin from baseline
Time frame: Baseline up to 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 5 | -82.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 9 | -139 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 13| | -121 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 17 | 16.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 21 | -95.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 5 | -38.0 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 9| | -144 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 13| | -155 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 17 | -123 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 21 | -291 ng/mL |
Secondary
Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
Absolute change in serum ferritin from baseline
Time frame: Baseline up 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 5 | -116 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 9 | -136 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 13 | 59.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Responders - Week 17 | 74.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 5 | -68.3 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 9 | -148 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 13 | 220.4 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 17 | -16.6 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) | Non-responders - Week 21 | -10.5 ng/mL |
Secondary
Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set)
Absolute change in serum ferritin from baseline
Time frame: Baseline up to 24 weeks
Population: Number of patients analyzed varied by visit
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 5 | -98.5 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 9 | -79.0 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 13 | 24.8 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 17 | -57.8 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Responders - Week 21 | -39.8 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 5 | -352 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 9 | -189 ng/mL |
| Erythropoietin Alpha | Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) | Non-responders - Week 13 | -44.5 ng/mL |
Secondary
Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set)
Erythroid response: hemoglobin increase from baseline \> = 1.5 g/dL (baseline \<11 g/dL)
Time frame: Week 13 up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erythropoietin Alpha | Summary of Erythroid Response in Participants Randomized to EPO Alone at Baseline and Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) | 0 participants |
Secondary
Summary of Erythroid Response Within 24 Weeks in Participants Randomized to EPO at Baseline and Not Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set)
Erythroid response: hemoglobin increase from baseline \> = 1.5 g/dL (baseline \<11 g/dL). Percentages are based on N. Confidence intervals are calculated using Clopper-Pearson method. Hemoglobin value is at time of first response
Time frame: baseline up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erythropoietin Alpha | Summary of Erythroid Response Within 24 Weeks in Participants Randomized to EPO at Baseline and Not Switched to EPO+DFX After 12 Weeks of Treatment (Full Analysis Set) | 71.4 percentage of participants |
Secondary
Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set)
Percentage of participants achieving an hematologic improvement defined as: neutrophil improvement: increase from baseline \>0.5 × 10\^9/L (baseline = 1.0 × 10\^9/L ), platelet improvement: increase from baseline ≥ 30 × 10\^9/L (baseline = 100 × 10\^9/L), hemoglobin improvement: Hb increase from baseline ≥ 1 g/dL (baseline\<11 g/dL)
Time frame: Baseline up to 24 weeks
Population: Number of patients who met criteria varied across parameters
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Hematologic improvement | 100 percentage of participants |
| Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Neutropil improvement | 66.7 percentage of participants |
| Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Platelet improvement | 50.0 percentage of participants |
| Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Hemoglobin improvement | 66.7 percentage of participants |
| Deferasirox + Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Hemoglobin improvement | 60.0 percentage of participants |
| Deferasirox + Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Hematologic improvement | 45.5 percentage of participants |
| Deferasirox + Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Platelet improvement | 80.0 percentage of participants |
| Deferasirox + Erythropoietin Alpha | Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) | Neutropil improvement | 80.0 percentage of participants |