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

NCT03920657 | Terminated Phase 2 DMC

• 1 other identifier: FISM_IRON-MDS
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Myelodysplastic Syndromes

Keywords

MDS

Outcome Measures

Primary Outcomes (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%

  1 year

Secondary Outcomes (10)

• Definition of iron overload

  1 year

• Efficacy of treatment

  1 year

• Evolution of iron overload serologic markers

  1 year

• Evolution of toxic serum iron forms

  1 year

• Relationship between NTBI and LPI with serum ferritin and liver and pancreas iron overload

  1 year

Study Arms (1)

Deferasirox

EXPERIMENTAL

patients will be assigned to a fixed dose of 3.5 mg/kg/day of DFX FCT.

Drug: Deferasirox

Interventions

Deferasirox DRUG

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

Also known as: Exjade

Deferasirox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Italiana Sindromi Mielodisplastiche-ETS: lead

Study Sites (10)

S.O.D. Ematologia Policlino Careggi

Florence, FI, 50134, Italy

Location

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

Orbassano, TO, 10043, Italy

Location

Ematologia - Spedali Civili

Brescia, 25100, Italy

Location

Ospedale Businco

Cagliari, Italy

Location

Ospedale San Martino

Genova, Italy

Location

Ospedale Niguarda

Milan, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

AO Bianchi Melacrino Morelli

Reggio Calabria, 89125, Italy

Location

Ospedale S. Eugenio

Roma, Italy

Location

Istituto clinico Humanitas

Rozzano (MI), Italy

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: April 19, 2019
• Study Start: October 4, 2019
• Primary Completion: October 6, 2020
• Study Completion: April 22, 2022
• Last Updated: November 21, 2022

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (10)