Trial Outcomes & Findings for Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients (NCT NCT00110266)

Last Updated: 2021-08-16

Results Overview

Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

176 participants

Primary outcome timeframe

up to 53 Weeks

Results posted on

2021-08-16

Participant Flow

The study was conducted at 39 centers in the United States and 6 centers in Canada

A total of 176 participants enrolled in the study, of these 173 participants were treated. Three of the enrolled participants were not treated as 2 withdrew the consent and 1 died even before initiating the treatment. Of the 173 treated participants, 95 completed the study and 78 discontinued treatment prematurely.

Participant milestones

Participant milestones
Measure	Deferasirox Participants received Deferasirox 20 Milligrams per Kilogram per day (mg/kg/day) orally once per day (OD) for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Overall Study STARTED	173
Overall Study COMPLETED	95
Overall Study NOT COMPLETED	78

Reasons for withdrawal

Reasons for withdrawal
Measure	Deferasirox Participants received Deferasirox 20 Milligrams per Kilogram per day (mg/kg/day) orally once per day (OD) for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Overall Study Adverse Event	27
Overall Study Abnormal laboratory value	15
Overall Study Withdrawal by Subject	16
Overall Study Death	17
Overall Study Unsatisfactory therapeutic effect	2
Overall Study Participant condition no longer requires study drug	1

Baseline Characteristics

Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Age, Continuous	69.9 years STANDARD_DEVIATION 11.45 • n=5 Participants
Sex: Female, Male Female	70 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	159 Participants n=5 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants
Race/Ethnicity, Customized Oriental	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 53 Weeks

Population: The safety population consisted of all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Number of Participants Reporting Adverse Events	171 Participants

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37 and 53

Population: The Full Analysis Set (FAS) populations consisted of all participants who received at least 1 dose of study drug.

Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).

Outcome measures

Outcome measures
Measure	Deferasirox n=172 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Baseline	2771.5 μg/L Interval 863.0 to 9993.0
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Week 13	-146.5 μg/L Interval -6679.0 to 3260.0
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Week 25	-167.5 μg/L Interval -5034.0 to 2265.0
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Week 37	-505.0 μg/L Interval -3699.0 to 4132.0
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 Week 53	-592.0 μg/L Interval -5752.0 to 5948.0

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37 and 49

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Change in Labile Plasma Iron (LPI) Baseline	0.30 LPI Unit Interval 0.0 to 3.6
Change in Labile Plasma Iron (LPI) Week 13	-0.10 LPI Unit Interval -3.3 to 2.2
Change in Labile Plasma Iron (LPI) Week 25	-0.20 LPI Unit Interval -2.4 to 1.2
Change in Labile Plasma Iron (LPI) Week 37	-0.30 LPI Unit Interval -3.4 to 0.6
Change in Labile Plasma Iron (LPI) Week 49	-0.45 LPI Unit Interval -3.6 to 0.9

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37 and 49

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Directly Chelatable Iron (DCI) Baseline	0.00 µM Interval 0.0 to 1.3
Directly Chelatable Iron (DCI) Week 13	0.00 µM Interval -0.5 to 2.2
Directly Chelatable Iron (DCI) Week 25	0.00 µM Interval -0.6 to 2.6
Directly Chelatable Iron (DCI) Week 37	0.00 µM Interval -0.6 to 1.4
Directly Chelatable Iron (DCI) Week 49	0.00 µM Interval -0.6 to 1.6

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37, 49 and 53

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Total Iron Levels Baseline	194.0 μg/dL Interval 48.0 to 409.0
Total Iron Levels Week 13	230.50 μg/dL Interval 54.0 to 863.0
Total Iron Levels Week 25	222.0 μg/dL Interval 27.0 to 497.0
Total Iron Levels Week 37	212.0 μg/dL Interval 53.0 to 480.0
Total Iron Levels Week 49	218.0 μg/dL Interval 48.0 to 929.0
Total Iron Levels Week 53	221.00 μg/dL Interval 16.0 to 455.0

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37, 49 and 53

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Serum Transferrin Levels Baseline	156.0 mg/dL Interval 83.0 to 244.0
Serum Transferrin Levels Week 13	161.0 mg/dL Interval 108.0 to 257.0
Serum Transferrin Levels Week 25	160.0 mg/dL Interval 107.0 to 266.0
Serum Transferrin Levels Week 37	158.0 mg/dL Interval 88.0 to 272.0
Serum Transferrin Levels Week 49	160.0 mg/dL Interval 90.0 to 289.0
Serum Transferrin Levels Week 53	161.00 mg/dL Interval 99.0 to 253.0

SECONDARY outcome

Timeframe: From Baseline to Weeks 13, 25, 37, 49 and 53

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Transferrin Saturation Baseline	91.00 percentage of saturation Interval 20.0 to 94.0
Transferrin Saturation Week 13	-11.00 percentage of saturation Interval -73.0 to 57.0
Transferrin Saturation Week 25	-11.00 percentage of saturation Interval -66.0 to 58.0
Transferrin Saturation Week 37	-12.50 percentage of saturation Interval -68.0 to 57.0
Transferrin Saturation Week 49	-12.00 percentage of saturation Interval -72.0 to 65.0
Transferrin Saturation Week 53	-18.00 percentage of saturation Interval -69.0 to 64.0

SECONDARY outcome

Timeframe: up to 1 year

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

Number of participants receiving transfusions, the summarized during the study.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Transfusion Requirements Screening	163 Participants
Transfusion Requirements Week 1 through 13	136 Participants
Transfusion Requirements Week 14 through 26	119 Participants
Transfusion Requirements Week 27 through 39	98 Participants
Transfusion Requirements Week 40 through 52	72 Participants

SECONDARY outcome

Timeframe: up to 1 year

Population: The analysis was performed on Per protocol population defined as number of participants who did not present any major deviations from protocol and received at least one dose of study drug.

Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as: Erythroid response (pretreatment, \<11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,\<100x10\^9/L): If starting with \>20x10\^9/L platelets: absolute increase 30x10\^9/L, Increase from baseline \<20 x10\^9/L to \>20x10\^9/L and by =/\> 100%; Neutrophil response (pretreatment, \<1.0x10\^9/L): =/\> 100% increase \& absolute increase \>0.5x10\^9/L; Progression or relapse after HI: At least 1 of the following: =/\>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.

Outcome measures

Outcome measures
Measure	Deferasirox n=91 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Frequency of Hematologic Improvement During the Study Response (Yes)	7 Participants
Frequency of Hematologic Improvement During the Study Response (No)	74 Participants
Frequency of Hematologic Improvement During the Study Missing	10 Participants

SECONDARY outcome

Timeframe: At Week 13, 25, 37 and 49

Population: The full analysis set populations consisted of all participants who received at least 1 dose of study drug.

The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Trough Plasma Deferasirox Concentration Week 13	21.200 μmol/L Interval 0.0 to 209.0
Trough Plasma Deferasirox Concentration Week 25	26.700 μmol/L Interval 0.0 to 331.0
Trough Plasma Deferasirox Concentration Week 37	25.200 μmol/L Interval 0.0 to 242.0
Trough Plasma Deferasirox Concentration Week 49	30.700 μmol/L Interval 0.0 to 223.0

SECONDARY outcome

Timeframe: up to 1 year

Population: The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.

Outcome measures

Outcome measures
Measure	Deferasirox n=173 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Treatment Compliance to Deferasirox 20 to < 40 %	2 participants
Treatment Compliance to Deferasirox 40 - < 60 %	1 participants
Treatment Compliance to Deferasirox 60 - < 80 %	4 participants
Treatment Compliance to Deferasirox 80 - < 100 %	89 participants
Treatment Compliance to Deferasirox 100 - < 120 %	65 participants
Treatment Compliance to Deferasirox ≥ 120 %	12 participants

SECONDARY outcome

Timeframe: up to Week 13 (Month 3)

Population: The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.

Outcome measures

Outcome measures
Measure	Deferasirox n=94 Participants Participants received Deferasirox 20 mg/kg/day orally OD for one year. The appropriate daily dose was calculated by participants actual body weight. Deferasirox was taken every morning 30 minutes before breakfast, preferably around the same time between 7:00 and 9:00 AM each day. The tablets was dropped into water or apple juice or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations C282Y · Negative	85 Participants
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations C282Y · Positive Heterozygous	9 Participants
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations H63D · Negative	70 Participants
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations H63D · Positive Heterozygous	24 Participants
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations S65C · Negative	92 Participants
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations S65C · Positive Heterozygous	2 Participants

Adverse Events

Deferasirox

Serious events: 78 serious events

Other events: 166 other events

Deaths: 17 deaths

Enrolled, Not Treated

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place