Phase 2
N=23
Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.
Low and Int 1-risk Myelodysplastic Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT01868477 ↗Enrolled (actual)
23
Serious AEs
17.4%
Results posted
Oct 2018
Primary outcome: Primary: Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) — 41.7; 27.3 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Deferasirox DFX, DT (Drug); Erythropoietin alpha (Drug); Deferasirox DFX, FCT (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Mar 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set) |
41.7; 27.3 | — |
| SECONDARY Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set) |
1.8; 2.1 | — |
| SECONDARY Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set) |
100; 45.5; 66.7; 80.0; 50.0; 80.0 | — |
| SECONDARY Absolute Change in Hemoglobin Values up to 24 Weeks |
1.3; 1.4 | — |
| SECONDARY Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks |
58.7; 66.3; 1.2; 2.4 | — |
| 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) |
— | — |
| 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) |
71.4 | — |
| SECONDARY Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set) |
-98.5; -79.0; 24.8; -57.8; -39.8; -352 | — |
| SECONDARY Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) |
-82.5; -139; -121; 16.5; -95.5; -38.0 | — |
| SECONDARY Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set) |
-116; -136; 59.5; 74.5; -68.3; -148 | — |
| SECONDARY Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set) |
1.5; 1.9; 1.7; 1.6; 0.8; -0.9 | — |
| SECONDARY Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set) |
0.7; 1.6; 2.9; 2.4; 1.7; -0.1 | — |
| SECONDARY Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set) |
1.2; 1.8; 0.7; -0.6; 0.3; 0.5 | — |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01868477). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.