Clinical Trials /

Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.

NCT01868477

Description:

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Completed

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT01868477

Trial Eligibility

Document

Title

  • Brief Title:Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.
  • Official Title:An Open-label, Phase II, Randomized, Pilot Study to Assess the Effect in Term of Erythroid Improvement of Deferasirox Combined With Erythropoietin Compared to Erythropoietin Alone in Patients With low-and Int-1-risk Myelodysplastic Syndrome.

Clinical Trial IDs

  • ORG STUDY ID: CICL670A2421
  • NCT ID: NCT01868477

Trial Conditions

  • Adult Patients With Low- and Int-1-risk Myelodysplastic Syndrome.

Trial Interventions

DrugSynonymsArms
Erythropoietin alphaErythropoietin alpha
Erythropoietin alphaDeferasirox + Erythropoietin alpha
DeferasiroxDeferasirox + Erythropoietin alpha

Trial Purpose

The primary purpose of this trial 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 could 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 is designed to test in a prospective way the combination of deferasirox with erythropoietin in term of their effect on hematopoiesis.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Erythropoietin alphaExperimentalPatients will receive erythropoietin 40,000 units/week. If after 4 weeks erythroid improvement is inadequate, dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be switched to the combination arm. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study.
  • Erythropoietin alpha
    Deferasirox + Erythropoietin alphaExperimentalPatients will receive 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 is inadequate, erythropoietin dose will be escalated to 60,000 units/week. If after 12 weeks of treatment, erythroid improvement in inadequate, patients will be discontinued from the study. At any time when erythroid response is achieved, erythropoietin treatment will be stopped until end of study. Patients will continue deferasirox treatment.
      • Erythropoietin alpha
      • Deferasirox

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with low- and Int-1-risk myelodysplastic syndrome

    - Documented diagnosis of the following:

    Myelodysplastic syndrome lasting ≥ 3 months and < 3 years Disease must not be 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 be 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 may be accepted at the investigator's discretion.

    - Endogenous erythropoietin levels < 500 units/L

    Exclusion Criteria:

    - Patients with 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 receiving 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 are allowed).

    - B12 and folate deficient patients with and without clinical symptoms (patients could be rescreened after successful therapy of B12 and folate deficiency)

    - Uncontrolled seizures or uncontrolled hypertension

    Other protocol-defined inclusion/exclusion criteria may apply.

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Change in hemoglobin levels
    Time Frame:Within 12 weeks
    Safety Issue:No
    Description:Difference in proportion of patients achieving an erythroid response within 12 weeks of treatment between the two arms according to modified IWG 2006 criteria (increase in Hb ≥ 1.5 g/dL)

    Secondary Outcome Measures

    Measure:Change in hemoglobin, platelets and neutrophil levels
    Time Frame:Within 24 weeks
    Safety Issue:No
    Description:Proportion of patients achieving a hematological response within 24 weeks of treatment with deferasirox combined with erythropoietin and erythropoietin alone (increase in hemoglobin, improvement of neutropenia and thrombocytopenia) according to modified IWG 2006 criteria
    Measure:Change in hemoglobin levels
    Time Frame:Within 24 weeks
    Safety Issue:No
    Description:Proportion of patients achieving an erythroid response according to modified IWG 2006 criteria (increase in Hb ≥ 1.5 g/dL) within 24 weeks
    Measure:Time to erythroid response
    Time Frame:up to 6 months
    Safety Issue:No
    Description:Time to response is defined as the time from date of start of treatment to the date of event defined as the first documented response according to modified IWG 2006 criteria (increase in Hb ≥ 1.5 g/dL)
    Measure:Time to hematologic response
    Time Frame:up to 6 months
    Safety Issue:No
    Description:Time to response is defined as the time from date of start of treatment to the date of event defined as the first documented response (increase in hemoglobin, improvement of neutropenia and thrombocytopenia) according to modified IWG 2006 criteria
    Measure:Duration of erythroid response
    Time Frame:up to 6 months
    Safety Issue:No
    Description:Duration of response is defined as the time from onset of the first response to progression/relapse (decrease in Hb ≥ 1.5 g/dL from Hb value at response)
    Measure:Number of adverse events (AEs) and serious adverse events (SAEs)
    Time Frame:up to 6 months
    Safety Issue:Yes
    Description:Incidence of adverse events (AEs) overall and by severity, and serious adverse events (SAEs)
    Measure:Iron parameters by change in serum ferritin
    Time Frame:Baseline, followed by evaluation after 1, 2, 3, 4, 5 and 6 months
    Safety Issue:No
    Description:Change in serum ferritin from baseline to every visit throughout the study in the combination arm
    Measure:Change in platelets and neutrophil levels
    Time Frame:Within 24 weeks
    Safety Issue:No
    Description:Proportion of patients achieving a hematological improvement within 24 weeks of treatment with deferasirox combined with erythropoietin and erythropoietin alone (improvement of neutropenia and thrombocytopenia)
    Measure:Time to hematologic improvement
    Time Frame:up to 6 months
    Safety Issue:No
    Description:Time to improvement is defined as the time from date of start of treatment to the date of event defined as the first documented improvement (improvement of neutropenia and thrombocytopenia)

    Trial Keywords