Clinical trial NCT03920657: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: MDS
Lead sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS
Sponsor class: OTHER
First posted: 2019-04-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change of hepatic iron
timeFrame: 1 year
Secondary outcomes:
measure: Definition of iron overload
timeFrame: 1 year
measure: Efficacy of treatment
timeFrame: 1 year
measure: Evolution of iron overload serologic markers
timeFrame: 1 year
measure: Evolution of toxic serum iron forms
timeFrame: 1 year
measure: Relationship between NTBI and LPI with serum ferritin and liver and pancreas iron overload
timeFrame: 1 year
measure: Overall safety of deferasirox
timeFrame: 1 year
measure: Leukemic transformation
timeFrame: 1 year
measure: Hemopoietic response
timeFrame: 1 year
measure: Costs analysis
timeFrame: 1 year
measure: Study of biological cellular damage
timeFrame: 1 year
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: S.O.D. Ematologia Policlino Careggi
state: FI
city: Orbassano
country: Italy
facility: Medicina Interna II Divisione di Ematologia, Ospedale S. Luigi Gonzaga
state: TO
city: Brescia
country: Italy
facility: Ematologia - Spedali Civili
city: Cagliari
country: Italy
facility: Ospedale Businco
city: Genova
country: Italy
facility: Ospedale San Martino
city: Milano
country: Italy
facility: Ospedale Niguarda
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Reggio Calabria
country: Italy
facility: AO Bianchi Melacrino Morelli
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Rozzano (MI)
country: Italy
facility: Istituto clinico Humanitas
Study officials:
References: