Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.
Condition: Low and Int 1-risk Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Deferasirox DFX, DT; Erythropoietin alpha; Deferasirox DFX, FCT
Intervention description: provided as dispersible tablets for oral use in 125 and 250, 500 mg; provided as film-coated tablet for oral use in 90, 180, 360 mg strengths
Intervention MeSH terms: Epoetin Alfa; Deferasirox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myelodysplastic syndrome; MDS; myelodysplasia; blood disorder; cytopenias; low blood counts; progressive bone marrow failure; adult; ICL570; deferasirox; erythropoietin; erythropoiesis; NF-kB pathway; hematopoiesis.

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