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Myelodysplastic SyndromesPhase 2NCT03920657

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

A Phase 2 study testing Deferasirox in people with Myelodysplastic Syndromes, run by Fondazione Italiana Sindromi Mielodisplastiche-ETS at 10 sites in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Deferasirox
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
10 sitesItaly
Study dates
4 Oct 2019to 22 Apr 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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).
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  • 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

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Italy10 sites

  • Ematologia - Spedali Civili

    Brescia, 25100

  • Ospedale Businco

    Cagliari

  • S.O.D. Ematologia Policlino Careggi

    Florence, FI, 50134

  • Ospedale San Martino

    Genova

  • Ospedale Niguarda

    Milan

  • Medicina Interna II Divisione di Ematologia, Ospedale S. Luigi Gonzaga

    Orbassano, TO, 10043

  • Azienda Ospedaliera di Padova

    Padova, 35128

  • AO Bianchi Melacrino Morelli

    Reggio Calabria, 89125

  • Ospedale S. Eugenio

    Roma

  • Istituto clinico Humanitas

    Rozzano (MI)

Other trials in Italy

About this study

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.

Read more

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.

Being tested
Deferasirox
Keywords
MDS
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DeferasiroxDrug

    Also called Exjade

    Fixed dose of 3.5 mg/kg/day of DFX FCT

Study groups in NCT03920657
Study groupRoleWhat they receive
DeferasiroxExperimentalpatients will be assigned to a fixed dose of 3.5 mg/kg/day of DFX FCT.
Receives: Drug: Deferasirox

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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%

    Measured: 1 year

Secondary outcomes (10)

  1. 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.

    Measured: 1 year

  2. Efficacy of treatment

    Absolute change in hepatic iron concentration EOS versus baseline.

    Measured: 1 year

  3. 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

    Measured: 1 year

  4. Evolution of toxic serum iron forms

    Presence and quantitative evolution of toxic serum iron forms (iron tissue reactive species) under low dose DFX therapy

    Measured: 1 year

  5. 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).

    Measured: 1 year

  6. 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

    Measured: 1 year

  7. Leukemic transformation

    Leukemic transformation (progression to leukemia or higher rIPSS scores)

    Measured: 1 year

  8. Hemopoietic response

    Percentage of patients with hematologic improvements in term of erythroid response following IWG 2006 criteria.

    Measured: 1 year

  9. 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.

    Measured: 1 year

  10. 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).

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2019
  2. Study start4 Oct 2019
  3. Primary completion6 Oct 2020
  4. Study completion22 Apr 2022

Why it stopped: enrollment failed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
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)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03920657
Sponsor's protocol ID
FISM_IRON-MDS
Status last verified
Mar 2021
First submitted
14 Dec 2018
Last updated
21 Nov 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Deferasirox in people with Myelodysplastic Syndromes, run by Fondazione Italiana Sindromi Mielodisplastiche-ETS at 10 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: enrollment failed). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of hepatic iron (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03920657.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2022; AzTrials last refreshed its copy on 7 Nov 2026.

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