Early and Low Dose Deferasirox (3.5 mg/kg FCT) to Suppress NTBI and LPI as Early Intervention to Prevent Tissue Iron Overload in Lower Risk MDS
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03920657|
Recruitment Status : Recruiting
First Posted : April 19, 2019
Last Update Posted : July 17, 2019
The scientific rationale for this study is the evolving understanding that iron-induced tissue damage is not only a process of progressive bulking of organs through high-volumes iron deposition, but also a reactive iron species related "toxic" damage.
Iron mediated damage can occur prior reaching high iron storage thresholds derived from thalassemia major setting, free toxic iron species being already present when transferrin saturation >60-70% (25); therefore a timely early adoption of iron chelation may be of benefit before overt iron overload is seen.
Our hypothesis is that early and low dose DFX-FCT is better tolerated and is able to prevent iron accumulation and consequently tissue iron related damage, by consistently suppressing iron reactive oxygen species (NTBI and LPI).
If this hypothesis is confirmed this approach could contribute to an improvement of clinical practice of patients managements. Additionally this approach might also be a contribute in preventing future iron overloaded related complication, in this already frail and co-treated patient population.
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Drug: Deferasirox||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is an open-label, single arm, phase II, study designed to look whether early intervention with low dose DFX improves clinical outcome of patients with MDS.|
|Masking:||None (Open Label)|
|Official Title:||Early and Low Dose Deferasirox (3.5 mg/kg FCT) to Suppress NTBI and LPI as Early Intervention to Prevent Tissue Iron Overload in Lower Risk MDS|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||January 2021|
patients will be assigned to a fixed dose of 3.5 mg/kg/day of DFX FCT.
Fixed dose of 3.5 mg/kg/day of DFX FCT
Other Name: Exjade
- Change of hepatic iron [ Time Frame: 1 year ]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%
- Definition of iron overload [ Time Frame: 1 year ]
The baseline iron status of MDS patients at the beginning of their transfusion story is today unknown. This study is the first unbiased and direct measurement of iron stress and oxidative stress in MDS patients at the beginning of the transfusion story.
Baseline iron status will be described by classical iron markers:
serum ferritin (ng/ml), transferritin saturation (%), liver and pancreas iron concentration by MRI (mg/g dry weight). Total body iron stores will be calculated (mg/kg) with the published formula (N Engl J Med 2000; 343:327-331).
Tissue reactive oxygen species will be measured in the patient's plasma as follows:
non-transferrin bound iron= micromoles/L, Labile Plasma Iron= micromoles/L. Oxidative stress will be measured by Malonildialdehyde (MDA). Levels in plasmas= micromoles/L.
- Efficacy of treatment [ Time Frame: 1 year ]Absolute change in hepatic iron concentration EOS versus baseline.
- Evolution of iron overload serologic markers [ Time Frame: 1 year ]Absolute and relative changes in serum ferritin and transferrin saturation from baseline to every visit during the whole treatment period
- Evolution of toxic serum iron forms [ Time Frame: 1 year ]Presence and quantitative evolution of toxic serum iron forms (iron tissue reactive species) under low dose DFX therapy
- Relationship between NTBI and LPI with serum ferritin and liver and pancreas iron overload [ Time Frame: 1 year ]
Prevention of iron overload will be studied by the difference iron parameters end of therapy - baseline by liver iron concentration (mg/g dry weight), pancreas iron concentration (mg/g dry weight), total body iron stores (mg/kg) calculated the N Engl J med 2000 343:327-331 formula = liver iron concentration x 10.6.
Serum ferritin = ng/ml.
Relationship between suppression of tissue iron species and prevention of iron accumulation (observational study) will be measured by the:
NTBI/LPI values (micromoles/L), Differences end of study - baseline quantitative parameters of iron loading (liver and pancreas iron concentration and total body iron stores).
- Overall safety of deferasirox [ Time Frame: 1 year ]Evaluate the overall safety of deferasirox FCT formulation in patients with lower risk MDS at the beginning of their transfusional history
- Leukemic transformation [ Time Frame: 1 year ]Leukemic transformation (progression to leukemia or higher rIPSS scores)
- Hemopoietic response [ Time Frame: 1 year ]Percentage of patients with hematologic improvements in term of erythroid response following IWG 2006 criteria.
- Costs analysis [ Time Frame: 1 year ]Treatment cost will be compared with standard approach cost (14 mg/kg/day. DFX-FCT after 20 units of packed red cells units and serum ferritin> 1000 ng/ml over one year of treatment). For comparison literature and matched FISM registry data will be used. Unit of measurement will be 2019 USD and Euros.
- Study of biological cellular damage [ Time Frame: 1 year ]Biological cellular damage will be measured by presence and level of oxidative stress determined at baseline, during and at end of study and compared with ongoing treatment by: Malonildialdehyde (MDA) plasma levels (micromoles/L).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03920657
|Contact: Emanuele Angelucci||+39 010 firstname.lastname@example.org|
|Contact: SEGRETERIA FISM||+39 0131 email@example.com|
|S.O.D. Ematologia Policlino Careggi||Not yet recruiting|
|Firenze, FI, Italy, 50134|
|Principal Investigator: Valeria Santini, Prof.|
|Medicina Interna II Divisione di Ematologia, Ospedale S. Luigi Gonzaga||Not yet recruiting|
|Orbassano, TO, Italy, 10043|
|Contact: Daniela Cilloni, MD +39 011-9026709 firstname.lastname@example.org|
|Principal Investigator: Daniela Cilloni, MD|
|Ematologia - Spedali Civili||Not yet recruiting|
|Brescia, Italy, 25100|
|Principal Investigator: Giuseppe Rossi, MD|
|Ospedale Businco||Not yet recruiting|
|Principal Investigator: Federica Pilo, MD|
|Ospedale San Martino||Recruiting|
|Principal Investigator: Emanuele Angelucci, MD|
|Ospedale Niguarda||Not yet recruiting|
|Principal Investigator: Marta Riva, MD|
|Azienda Ospedaliera di Padova||Not yet recruiting|
|Padova, Italy, 35128|
|Principal Investigator: Gianni Binotto, MD|
|AO Bianchi Melacrino Morelli||Not yet recruiting|
|Reggio Calabria, Italy, 89125|
|Principal Investigator: Ester Oliva, MD|
|Ospedale S. Eugenio||Not yet recruiting|
|Principal Investigator: Pasquale Niscola, MD|
|Istituto clinico Humanitas||Not yet recruiting|
|Rozzano (MI), Italy|
|Principal Investigator: Matteo Della Porta, Prof.|