Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03920657
Other study ID # FISM_IRON-MDS
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date October 4, 2019
Est. completion date April 22, 2022

Study information

Verified date March 2021
Source Fondazione Italiana Sindromi Mielodisplastiche-ETS
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Terminated
Enrollment 11
Est. completion date April 22, 2022
Est. primary completion date October 6, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Diagnosis: Adult Myelodysplastic Syndrome (=18 years). - Revised IPSS: very low. low - intermediate - Having received 5-20 packed red blood cell units - Serum ferritin =300 ng/ml - Transferrin saturation = 60% - Chelation naïve - Capability to provide informed consent Exclusion Criteria: - Patients aged <18 years old - Higher risk (revised IPSS) MDS (Intermediate 2, high) - Cumulative transfusion story of > 20 packed red cell units - Creatinine Clearance (CrCL): <60 ml/min. Patients with CrCl of 40-60ml/min will be included only individually if no other renal risk factors are present. - Serum creatinine >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. - 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). - ECOG performance status >2. - Left ventricular ejection fraction < 50% by echocardiography - A history of repeated hospitalization for congestive heart failure. - Systemic diseases that would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.) - Clinical or laboratory evidence of chronic Hepatitis B or Hepatitis C (definition of chronic hepatitis follows EASL 2017 criteria). - History of HIV positive test result (ELISA or Western blot). - Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start. - ALT or AST over 3 times superior to ULN at screening. - ANC < 500/ microL - Platelets transfusion dependency - Total bilirubin over 1.5 times superior to ULN at screening (patients with Gilbert syndrome are allowed to enter the study) - Diagnosis of Child score C liver cirrhosis. - Patients participating in another clinical trial other than an observational registry study. - 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. - History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative. - Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug. - Pregnant, intending-to-become pregnant, or breast-feeding patients. - Women of potential maternity age who do not agree to practice effective contraceptive methods fo the entire study duration. - History of drug or alcohol abuse within the 12 months prior to enrollment. - Hypersensitivity to the active substance or to any of the excipients. - Inability to provide a valid informed consent

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Deferasirox
Fixed dose of 3.5 mg/kg/day of DFX FCT

Locations

Country Name City State
Italy Ematologia - Spedali Civili Brescia
Italy Ospedale Businco Cagliari
Italy S.O.D. Ematologia Policlino Careggi Firenze FI
Italy Ospedale San Martino Genova
Italy Ospedale Niguarda Milano
Italy Medicina Interna II Divisione di Ematologia, Ospedale S. Luigi Gonzaga Orbassano TO
Italy Azienda Ospedaliera di Padova Padova
Italy AO Bianchi Melacrino Morelli Reggio Calabria
Italy Ospedale S. Eugenio Roma
Italy Istituto clinico Humanitas Rozzano (MI)

Sponsors (1)

Lead Sponsor Collaborator
Fondazione Italiana Sindromi Mielodisplastiche-ETS

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change of hepatic iron 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% 1 year
Secondary Definition of iron overload 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.
1 year
Secondary Efficacy of treatment Absolute change in hepatic iron concentration EOS versus baseline. 1 year
Secondary Evolution of iron overload serologic markers Absolute and relative changes in serum ferritin and transferrin saturation from baseline to every visit during the whole treatment period 1 year
Secondary Evolution of toxic serum iron forms Presence and quantitative evolution of toxic serum iron forms (iron tissue reactive species) under low dose DFX therapy 1 year
Secondary Relationship between NTBI and LPI with serum ferritin and liver and pancreas iron overload 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).
1 year
Secondary Overall safety of deferasirox Evaluate the overall safety of deferasirox FCT formulation in patients with lower risk MDS at the beginning of their transfusional history 1 year
Secondary Leukemic transformation Leukemic transformation (progression to leukemia or higher rIPSS scores) 1 year
Secondary Hemopoietic response Percentage of patients with hematologic improvements in term of erythroid response following IWG 2006 criteria. 1 year
Secondary Costs analysis 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. 1 year
Secondary Study of biological cellular damage 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). 1 year
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Terminated NCT04313881 - Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) Phase 3
Recruiting NCT05088356 - Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft Phase 1
Recruiting NCT04003220 - Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Active, not recruiting NCT03755414 - Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation Phase 1
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT04866056 - Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF. Phase 1/Phase 2
Recruiting NCT04701229 - Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
Suspended NCT04485065 - Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS Phase 1
Recruiting NCT04174547 - An European Platform for Translational Research in Myelodysplastic Syndromes
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Completed NCT02508870 - A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes Phase 1
Completed NCT04543305 - A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies Phase 1
Recruiting NCT05384691 - Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions Phase 2
Recruiting NCT05365035 - A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts Phase 2
Recruiting NCT06008405 - Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy Phase 1
Not yet recruiting NCT05969821 - Clonal Hematopoiesis of Immunological Significance
Withdrawn NCT05170828 - Cryopreserved MMUD BM With PTCy for Hematologic Malignancies Phase 1