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.
This study was designed to test in a prospective way the combination of deferasirox with erythropoietin in terms of their effect on hematopoiesis.
Brief Title
Combination Study of Deferasirox and Erythropoietin in Patients With Low- and Int-1-risk Myelodysplastic Syndrome.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Low and Int 1-risk Myelodysplastic Syndrome
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
myelodysplastic syndrome
MDS
myelodysplasia
blood disorder
cytopenias
low blood counts
progressive bone marrow failure
adult
ICL570
deferasirox
erythropoietin
erythropoiesis
NF-kB pathway
hematopoiesis.
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01868477
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CICL670A2421
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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.
Primary Outcomes
Outcome Description
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
Outcome Measure
Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set)
Outcome Time Frame
Baseline up to 12 weeks
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set)
Outcome Description
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)
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set)
Outcome Description
Absolute change in hemoglobin values for patients showing improvement: Hemoglobin improvement Hb increase from baseline ≥ 1 g/dL (baseline\<11 g/dL)
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Hemoglobin Values up to 24 Weeks
Outcome Description
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)
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks
Outcome Description
Erythroid response: hemoglobin increase from baseline \> = 1.5 g/dL (baseline \<11 g/dL)
Outcome Time Frame
Week 13 up to 24 weeks
Outcome Measure
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)
Outcome Description
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
Outcome Time Frame
baseline up to 24 weeks
Outcome Measure
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)
Outcome Description
Absolute change in serum ferritin from baseline
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set)
Outcome Description
Absolute change in serum ferritin from baseline
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
Outcome Description
Absolute change in serum ferritin from baseline
Outcome Time Frame
Baseline up 24 weeks
Outcome Measure
Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
Outcome Description
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.
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set)
Outcome Description
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.
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
Outcome Description
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.
Outcome Time Frame
Baseline up to 24 weeks
Outcome Measure
Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Olga Derman
Investigator Email
ODERMAN@montefiore.org
Investigator Phone
Categories Mesh Debug
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC SYNDROMES
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
Blood Disorders --- ANEMIA
Blood & Bone Marrow Cancers --- ANEMIA
MeSH Terms
MYELODYSPLASTIC SYNDROMES
ANEMIA, REFRACTORY, WITH EXCESS OF BLASTS
HEMATOLOGIC DISEASES
CYTOPENIA
BONE MARROW DISEASES
HEMIC AND LYMPHATIC DISEASES
ANEMIA, REFRACTORY
ANEMIA
DEFERASIROX
EPOETIN ALFA
BENZOATES
ACIDS, CARBOCYCLIC
CARBOXYLIC ACIDS
ORGANIC CHEMICALS
BENZENE DERIVATIVES
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
TRIAZOLES
AZOLES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ERYTHROPOIETIN
COLONY-STIMULATING FACTORS
GLYCOPROTEINS
GLYCOCONJUGATES
CARBOHYDRATES
HEMATOPOIETIC CELL GROWTH FACTORS
CYTOKINES
INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS
PROTEINS
BIOLOGICAL FACTORS