Adult patients with low risk MDS MedDRA version: 20.0 Level: LLT Classification code 10028532 Term: Myelodysplasia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: EXJADE - 180 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTERS PVC/PVDC/ALLUMINIO - 30 COMPRESSE
Product Name: Exjade
Product Code: [Agenti chelanti del ferro]
Pharmaceutical Form:
Sponsors
FONDAZIONE ITALIANA SINDROMI MIELODISPLASTICHE ETS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Diagnosis: Adult Myelodysplastic Syndrome (=18 years) 2) Revised IPSS: very low. low – intermediate 3) Having received 5-20 packed red blood cell units 4) Serum ferritin =300 ng/ml 5) Transferrin saturation =60% 6) Chelation naïve 7) Capability to provide informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1) Patients aged 20 packed red cell units 4) Creatinine Clearance (CrCL): 2 x ULN at screening. If borderline serum creatinine will be measured within 7-10 days and the mean value will be used for eligibility criteria 6) Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample (or alternatively in two of three samples obtained for screening) 7) ECOG performance status >2. 8) Left ventricular ejection fraction < 50% by echocardiograph 9) A history of repeated hospitalization for congestive heart failure. 10) Systemic diseases that would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.) 11) Clinical or laboratory evidence of chronic Hepatitis B or Hepatitis C (definition of chronic hepatitis follows EASL 2017 criteria) 12) History of HIV positive test result (ELISA or Western blot) 13) Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start. 14) ALT or AST over 3 times superior to ULN at screening 15) ANC < 500/ microL 16) Platelets transfusion dependency 17) Total bilirubin over 1.5 times superior to ULN at screening (patients with Gilbert syndrome are allowed to enter the study) 18) Diagnosis of Child score C liver cirrhosis 19) Patients participating in another clinical trial other than an observational registry study 20) Patients with a history of another malignancy within the past 3 years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ 21) History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative 22) Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug 23) Pregnant, intending-to-become pregnant, or breast-feeding patients 24) History of drug or alcohol abuse within the 12 months prior to enrollment 25) Inability to provide a valid informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Balance iron burden in one-year treatment in early phase of transfusion requirement by low dose (3.5 mg/kg) DFX-FCT (prevention of iron overload) as demonstrated by hepatic iron concentration.;Secondary Objective: 1) Definition of iron overload (including serological markers and MRI definition of iron loading in liver, tissue reactive iron species and oxidative stress in MDS at beginning of transfusional history 2) Efficacy 3) On year evolution of iron overload serologic markers 4) Presence and quantitative evolution of toxic serum iron forms (iron tissue reactive species) under low dose DFX therapy 5) Verify if regular suppression of the “free iron forms” prevent accumulation of tissue iron 6) Evaluate the overall safety of deferasirox FCT formulation in patients with lower risk MDS at the beginning of their transfusional history 7) Leukemic transformation (including progression to leukemia or higher rIPSS scores) 8) Hemopoietic response 9) Costs analysis 10) Study of biological cellular damage by iron toxicity before and during treatment;Primary end point(s): Change of hepatic iron from the baseline according to baseline hepatic iron level: For patients with baseline LIC = 5 mg/g dry weight (dw) ± 1.5 mg/g dw. For patients with baseline LIC >5 mg/g dw ±20% as demonstrated by R2- MRI (test performed in a 1.5 tesla MRI machine and analyzed following R2 method – Baseline versus EOS. The corresponding secondary efficacy variable will be the absolute change in hepatic iron concentration EOS versus baseline.;Timepoint(s) of evaluation of this end point: 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Absolute change in hepatic iron concentration EOS versus baseline.; Absolute and relative changes in serum ferritin and transferrin saturation from baseline to every visit during the whole treatment period.; Proportion of patients with NTBI > normal values and/or LPI > normal values at end of study vs baseline. Changes in NTBI and LPI from baseline to every visit during the whole treatment period.; Cost and outcome with low dose in early chelation vs. chelation treatment in MDS patients with transfusional iron overload in accordance with either local or international guidelines; MDA values during the study and relationship to NTBI and LPI values; Proportion of patients with a disease progression (progression defined as a transition into a higher MDS risk group based on revised IPSS scoring or progression to AML) Time to progression (defined as above) or to leukemia transformation.; Percentage of patients with hematologic improvements in term of erythroid response following IWG 2006 criteria. Time to reach transfusion dependence defined as > 2 PRBC units/months for 3 months for patients with pre-transfusional Hb < 9.0 g/dl (or <10 g/dl for patients with cardiac disease) or a total number of PRBC units received = 20 from baseline. Absolute reticulocytes count from baseline to every visit during the whole treatment period. Absolute values and evolution of serum transferrin receptor, GDF11, GDF15 and erythroferrone from baseline to every visit during the whole treatment period. Evaluation of transfusional ratio: number of units received in a predetermined period/ mean pretransfusional Hb level. Compared with other studies on general population (study and FISM registry). Patients receiving concurrent rHuEpo and other disease modifying agents will not be considered for hemopoietic response.; Overall safety, as measured by frequency and severity of reported AEs and SAEs and changes in laboratory values from baseline: serum creatinine, creatinine cle | — |
Countries
Italy
Contacts
Public ContactSegreteria
Fondazione Italiana Sindromi Mielodisplastiche Onlus
Outcome results
None listed