Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-Risk and INT-1 Myelodysplastic Patients

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00117507

Enrollment

Registered

2005-07-07

Start date

2005-09-30

Completion date

2008-01-31

Last updated

2021-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Iron Overload, Myelodysplastic Syndromes

Keywords

MDS, Myelodysplastic Syndrome, ICL-670, ICL-670 and Myelodysplastic Syndrome

Brief summary

Thirty patients were to be enrolled and 24 patients were actually enrolled into this open-label, single-arm trial designed to assess the safety and tolerability of oral deferasirox in adult transfusion dependent myelodysplastic syndrome (MDS) patients with iron overload. Patients enrolled in this study had low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria. All patients initiated treatment with 20mg/kg/day deferasirox. Deferasirox were administered orally once per day for 12 months.

Detailed description

Patients were screened for eligibility to determine if they meet all inclusion/exclusion criteria. The screening period were up to 4 weeks. Patient's baseline LIC will be determined non-invasively by means of MRI R2 analysis. In addition, blood and urine samples will be taken for the determination of baseline safety data.

Interventions

DRUGDeferasirox

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female patients with low or intermediate (INT-1) risk MDS, determined via IPSS criteria, with transfusional iron overload. NOTE: Bone marrow morphology and cytogenetic studies completed within 3 months prior to screening can be used if the patient has been hematologically stable. Every attempt to obtain cytogenetics studies should be made; however, if there is culture failure, repeat marrow aspiration will not be mandated. In this case, RAEB with less than 11% marrow blasts will be accepted. * Patients on chelation therapy at the time of screening required a 1-day wash out prior to the first dose of study drug. * Age: greater than or equal to 18 years * Serum ferritin: * For entry into the screening period: serum ferritin greater than or equal to 1000 µg/mL on at least two occasions, at least two weeks apart, during the prior year. Samples must be obtained in the absence of concomitant infection; * For enrollment into the study: serum ferritin greater than or equal to 1000 µg/mL at screening (via the central lab) obtained in the absence of concomitant infection * A lifetime minimum of 20 previous packed red cell transfusions * Life expectancy greater than or equal to 6 months * Women must have a negative serum or urine pregnancy test and use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined by amenorrhea for at least 12 months). * Able to provide written informed consent

Exclusion criteria

* Serum creatinine greater than 2 × upper limit of normal (ULN) * ALT or AST greater than 5 × ULN. * Clinical or laboratory evidence of active hepatitis B or hepatitis C (HBsAg in the absence of HBsAb -OR- HCV Ab positive with HCV RNA positive and ALT above the normal range) * Significant proteinuria as indicated by a urinary protein/creatinine ratio greater than 0.5 mg/mg in a non-first void urine sample during screening (or alternatively in two of three samples obtained for screening) * History of HIV positive test result (ELISA or Western blot) * ECOG performance status greater than 2 * Uncontrolled systemic hypertension * Unstable cardiac disease not controlled by standard medical therapy * Third degree atrioventricular (AV) block or QT interval prolongation above the normal range * History of clinically relevant ocular toxicity related to iron chelation * Pregnancy or breast feeding * Treatment with a systemic investigational drug within the past 4 weeks or a topical investigational drug within the past 7 days. * Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following: * inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding; * major gastrointestinal tract surgery, such as gastrectomy, gastroenterostomy, or bowel resection; * pancreatic injury or pancreatitis or indications of impaired pancreatic function/injury, as indicated by abnormal lipase or amylase; * urinary obstruction or difficulty in voiding. * History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Adverse Events and Serious Adverse Events	Up To Week 52	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Any sign or symptom that occured from first dose of study treatment until end of study treatment.

Secondary

Measure	Time frame	Description
Absolute Change in Liver Iron Concentration (LIC) From Baseline to End of Study	Baseline to Week 52	LIC was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2).
To Evaluate Change in Transfusion Requirements	Baseline to Week 52	Change in transfusion requirements from baseline.
Absolute Change in Serum Erythropoietin	Baseline to Week 52	Absolute Change in Serum Erythropoietin from baseline.
Absolute Change in Serum Ferritin From Baseline to Week 52	Baseline to Week 52	Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670).
Absolute Change in Transferrin Saturation	Baseline to Week 52	Transferrin Saturation was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2)
Labile Plasma Iron (LPI)	Baseline to Week 52	LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The outcome was reported as LPI Unit, where, 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe.
Absolute Change in Urinary Hepcidin	Baseline to Week 52	Absolute Change in Urinary Hepcidin from baseline

Countries

United States

Participant flow

Recruitment details

The study enrolled participants at 3 centers in United States.

Pre-assignment details

A total 24 participants were enrolled in the study of which 9 participants completed the study and 15 participants discontinued from the study.

Participants by arm

Arm	Count
Deferasirox Participants received deferasirox 20mg/kg/day OD per day for 12 months.	24
Total	24

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Abnormal laboratory values	3
Overall Study	Adverse Event	4
Overall Study	Death	3
Overall Study	Patient withdrew consent	4
Overall Study	Unsatisfactory therapeutic effect	1

Baseline characteristics

Characteristic	Deferasirox
Age, Continuous	68.6 years STANDARD_DEVIATION 8.58
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	16 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	3 / 24
other Total, other adverse events	23 / 24
serious Total, serious adverse events	11 / 24

Outcome results

Primary

Number of Participants With Adverse Events and Serious Adverse Events

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Any sign or symptom that occured from first dose of study treatment until end of study treatment.

Time frame: Up To Week 52

Population: The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-baseline safety assessment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Deferasirox	Number of Participants With Adverse Events and Serious Adverse Events	Adverse events	24 Participants
Deferasirox	Number of Participants With Adverse Events and Serious Adverse Events	Serious adverse events	11 Participants

Secondary

Absolute Change in Liver Iron Concentration (LIC) From Baseline to End of Study

LIC was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2).