Clinical trial NCT01868477: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low and Int 1-risk Myelodysplastic Syndrome
Keywords: myelodysplastic syndrome
MDS
myelodysplasia
blood disorder
cytopenias
low blood counts
progressive bone marrow failure
adult
ICL570
deferasirox
erythropoietin
erythropoiesis
NF-kB pathway
hematopoiesis.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-06-04
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Difference in Percentage of Patients Achieving Erythroid Response Within 12 Weeks, by Treatment Group (Full Analysis Set)
timeFrame: Baseline up to 12 weeks
Secondary outcomes:
measure: Absolute Change From Baseline to Post-baseline Value for Hemoglobin(g/dL)(Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Summary of Hematologic Improvement in Patients Randomized to EPO+DFX and EPO Alone, Within 24 Weeks of Treatment (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Hemoglobin Values up to 24 Weeks
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Platelets and Neutrophil Levels up to 24 Weeks
timeFrame: Baseline up to 24 weeks
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)
timeFrame: Week 13 up to 24 weeks
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)
timeFrame: baseline up to 24 weeks
measure: Absolute Change in Serum Ferritin up to 24 Weeks for Erythropoietin Alpha Arm (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Serum Ferritin up to 24 Weeks for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Serum Ferritin up to 24 Weeks for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
timeFrame: Baseline up 24 weeks
measure: Absolute Change in Hemoglobin (Hb) From Baseline for Erythropoietin Alpha Arm (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Hemoglobin (Hb) From Baseline for Deferasirox + Erythropoietin Alpha Arm (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
measure: Absolute Change in Hemoglobin (Hb) From Baseline for EPO+DFX at 12 Weeks Arm (Full Analysis Set)
timeFrame: Baseline up to 24 weeks
Other outcomes:
Locations:
city: Oran
country: Algeria
facility: Novartis Investigative Site
city: Sidi Bel abbes
country: Algeria
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Lütten-Klein
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
state: RC
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Girona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Gothenburg
country: Sweden
facility: Novartis Investigative Site
city: Linköping
country: Sweden
facility: Novartis Investigative Site
city: Lulea
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Oldham
country: United Kingdom
facility: Novartis Investigative Site
state: Lancashire
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: