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Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional Hemosiderosis

Primary Purpose

Chronic Anemia, Transfusional Hemosiderosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Deferasirox (ICL670)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Anemia focused on measuring Iron Overload,, Chelation,, MDS,, Chronic Anemia,, Deferasirox,, Transfusional hemosiderosis,

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria (Core):

  • Patients with transfusional iron overload due to:
  • low or intermediate (INT-1) risk Myelodysplastic Syndrome (MDS)determined via International Prognosis Scoring System (IPSS) criteria
  • other congenital or acquired anemias excluding B-thalassemia and sickle cell disease
  • Lifetime transfusion history of ≥20 unit (approximately 100 mL/kg) of packed red blood cells or showing evidence of iron overload (serum ferritin >1000 µg/L).
  • Able to provide written informed consent
  • Life expectancy ≥ 12 months If patient was previously treated with deferiprone, a washout period of one month should occur before the first dose of deferasirox

Inclusion criteria (Extension):

  • Patients completing the planned 12-month core study (CICL670A2204).
  • Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with national legislation.

Exclusion criteria (Core and Extension):

  • Patients with β-thalassemia, sickle cell disease or myelodysplastic syndrome with an IPSS score being Intermediate-2 or High.
  • Patients with serum creatinine > ULN
  • Patients with ALT(SGPT) levels > 5 x ULN
  • Significant proteinuria as indicated by a urinary protein/creatinine ratio >0.5 mg/mg in a non-first void urine sample on two assessments during the screening period.
  • History of HIV positive test result , or of 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)
  • Patients on investigational MDS therapies, including lenalidomide, thalidomide, azacitidine and arsenic trioxide, must have a ≥ 4 week washout period prior to the first dose of study drug.
  • Patients with systemic uncontrolled hypertension
  • Patients with unstable cardiac disease not controlled by standard medical therapy
  • Systemic disease (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
  • Pregnancy (as documented in required screening laboratory test) or breast feeding.
  • Patients treated with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days
  • Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug
  • Patients being considered by the investigator potentially unreliable and/or not cooperative with regard to the study protocol
  • History of hypersensitivity to any of the study drug or excipients
  • Sexually active pre-menopausal female patients without adequate contraception. Female patients must use effective contraception or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.

Other protocol defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deferasirox

Arm Description

Participants received initial dose of 20 milligrams per kilogram (mg/kg) Deferasirox tablets was administered orally once daily (OD) based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.

Outcomes

Primary Outcome Measures

Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1
Liver iron concentration (LIC), a predictor of iron burden, was measured using relaxation rate magnetic resonance imaging (R2-MRI) technique. Relaxation rate was determined as R2 = 1/relaxation time (T2). The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 milligram of iron/tissue dry weight (mg Fe/g dw). A negative change from baseline favored study treatment in reducing LIC.

Secondary Outcome Measures

Absolute Change From Baseline in Liver Iron Concentration (LIC) to End of Year 2
Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Absolute Change From Baseline in Liver Iron Concentration (LIC) in Japanese Subgroup
Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Absolute Change From Baseline in Serum Ferritin Levels to Year 2
Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Absolute Serum Ferritin Levels Over 2 Years
Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Total Body Iron Elimination Rate (TBIE), Iron Intake, Iron Excretion/Iron Intake and Chelation Efficiency After 2 Years
Total body iron excretion (TBIE)was used to investigate the chelation efficacy of Deferasirox therapy. TBIE rate was estimated based on the iron influx as determined by the amount of red cells transfused and the change in total body iron (TBI) stores.
Correlation of LIC and Serum Ferritin at Core and Extension Study
LIC, a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content. The correlation between absolute change in LIC and absolute change in serum ferritin was determined.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESI), Discontinuation and Interruption
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. Death was defined as a fatal event leading to permanent cessation of all vital functions of the body.
Number of Participants With Clinically Significant Ophthalmological Abnormalities
Clinically significant changes in left eye and right eye were assessed by the investigator based on methods like visual acuity, slit lamp examination, tonometry and fundus oculi.

Full Information

First Posted
February 27, 2008
Last Updated
June 4, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00631163
Brief Title
Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional Hemosiderosis
Official Title
A Multi-Center, Open-label, Non Comparative, Phase II Trial on Efficacy and Safety of ICL670 Given for 1 Year With Dose Adjustments Based on Serum Ferritin in Patients With Chronic Anemia and Transfusional Hemosiderosis Including an Additional 1 Year Extension.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The overall purpose of this trial is to further evaluate the efficacy and safety of deferasirox, dosed initially according to the transfusional iron intake, in patients with transfusion dependant anemia related to disorders other than β-thalassemia and sickle cell disease. During the study, the dose will be adjusted based on serum Ferritin.The overall purpose of the extension is to allow further treatment of patients who have already completed the core study, and to enable collection of long term efficacy and safety data. Patients will continue to receive Deferasirox at the dose they received at the end of the core study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Anemia, Transfusional Hemosiderosis
Keywords
Iron Overload,, Chelation,, MDS,, Chronic Anemia,, Deferasirox,, Transfusional hemosiderosis,

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
102 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
Participants received initial dose of 20 milligrams per kilogram (mg/kg) Deferasirox tablets was administered orally once daily (OD) based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Intervention Type
Drug
Intervention Name(s)
Deferasirox (ICL670)
Other Intervention Name(s)
ICL670
Intervention Description
The recommended initial daily dose of Deferasirox is 20 mg/kg body weight.
Primary Outcome Measure Information:
Title
Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1
Description
Liver iron concentration (LIC), a predictor of iron burden, was measured using relaxation rate magnetic resonance imaging (R2-MRI) technique. Relaxation rate was determined as R2 = 1/relaxation time (T2). The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 milligram of iron/tissue dry weight (mg Fe/g dw). A negative change from baseline favored study treatment in reducing LIC.
Time Frame
From the Baseline, Year 1 (End of core study)
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline in Liver Iron Concentration (LIC) to End of Year 2
Description
Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Time Frame
From the Baseline to End of Year 2 (End of extension study)
Title
Absolute Change From Baseline in Liver Iron Concentration (LIC) in Japanese Subgroup
Description
Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Time Frame
From the Baseline, End of Year 1 (End of core study), End of Year 2 (End of extension study)
Title
Absolute Change From Baseline in Serum Ferritin Levels to Year 2
Description
Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Time Frame
From the Baseline up to Year 2 (End of extension study)
Title
Absolute Serum Ferritin Levels Over 2 Years
Description
Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Time Frame
From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)
Title
Total Body Iron Elimination Rate (TBIE), Iron Intake, Iron Excretion/Iron Intake and Chelation Efficiency After 2 Years
Description
Total body iron excretion (TBIE)was used to investigate the chelation efficacy of Deferasirox therapy. TBIE rate was estimated based on the iron influx as determined by the amount of red cells transfused and the change in total body iron (TBI) stores.
Time Frame
From the Baseline, Year 2 (End of extension study)
Title
Correlation of LIC and Serum Ferritin at Core and Extension Study
Description
LIC, a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content. The correlation between absolute change in LIC and absolute change in serum ferritin was determined.
Time Frame
From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESI), Discontinuation and Interruption
Description
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. Death was defined as a fatal event leading to permanent cessation of all vital functions of the body.
Time Frame
From the Baseline up to Year 2 (End of extension study)
Title
Number of Participants With Clinically Significant Ophthalmological Abnormalities
Description
Clinically significant changes in left eye and right eye were assessed by the investigator based on methods like visual acuity, slit lamp examination, tonometry and fundus oculi.
Time Frame
At 2 years (End of extension study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria (Core): Patients with transfusional iron overload due to: low or intermediate (INT-1) risk Myelodysplastic Syndrome (MDS)determined via International Prognosis Scoring System (IPSS) criteria other congenital or acquired anemias excluding B-thalassemia and sickle cell disease Lifetime transfusion history of ≥20 unit (approximately 100 mL/kg) of packed red blood cells or showing evidence of iron overload (serum ferritin >1000 µg/L). Able to provide written informed consent Life expectancy ≥ 12 months If patient was previously treated with deferiprone, a washout period of one month should occur before the first dose of deferasirox Inclusion criteria (Extension): Patients completing the planned 12-month core study (CICL670A2204). Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with national legislation. Exclusion criteria (Core and Extension): Patients with β-thalassemia, sickle cell disease or myelodysplastic syndrome with an IPSS score being Intermediate-2 or High. Patients with serum creatinine > ULN Patients with ALT(SGPT) levels > 5 x ULN Significant proteinuria as indicated by a urinary protein/creatinine ratio >0.5 mg/mg in a non-first void urine sample on two assessments during the screening period. History of HIV positive test result , or of 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) Patients on investigational MDS therapies, including lenalidomide, thalidomide, azacitidine and arsenic trioxide, must have a ≥ 4 week washout period prior to the first dose of study drug. Patients with systemic uncontrolled hypertension Patients with unstable cardiac disease not controlled by standard medical therapy Systemic disease (cardiovascular, renal, hepatic, etc.) which would prevent study treatment Pregnancy (as documented in required screening laboratory test) or breast feeding. Patients treated with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug Patients being considered by the investigator potentially unreliable and/or not cooperative with regard to the study protocol History of hypersensitivity to any of the study drug or excipients Sexually active pre-menopausal female patients without adequate contraception. Female patients must use effective contraception or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months. Other protocol defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmeceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
453-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka-city
State/Province
Fukuoka
ZIP/Postal Code
814-0180
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo-city
State/Province
Hokkaido
ZIP/Postal Code
060-8543
Country
Japan
Facility Name
Novartis Investigative Site
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Facility Name
Novartis Investigative Site
City
Kahoku-gun
State/Province
Ishikawa
ZIP/Postal Code
920-0293
Country
Japan
Facility Name
Novartis Investigative Site
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Novartis Investigative Site
City
OsakaSayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita-city
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Shimotsuka-gun
State/Province
Tochigi
ZIP/Postal Code
321-0293
Country
Japan
Facility Name
Novartis Investigative Site
City
Simotsuke-city
State/Province
Tochigi
ZIP/Postal Code
329-0498
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Cyuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Minato-ku
State/Province
Tokyo
ZIP/Postal Code
108-8639
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinagawa-ku
State/Province
Tokyo
ZIP/Postal Code
141-8625
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
162-8666
Country
Japan
Facility Name
Novartis Investigative Site
City
Hiroshima
ZIP/Postal Code
734-8551
Country
Japan
Facility Name
Novartis Investigative Site
City
Kumamoto
ZIP/Postal Code
860-0811
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagasaki
ZIP/Postal Code
852-8501
Country
Japan
Facility Name
Novartis Investigative Site
City
Toyama
ZIP/Postal Code
930-8550
Country
Japan
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
26138856
Citation
Kohgo Y, Urabe A, Kilinc Y, Agaoglu L, Warzocha K, Miyamura K, Lim LC, Glaser S, Wang C, Wiktor-Jedrzejczak W. Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias. Acta Haematol. 2015;134(4):233-42. doi: 10.1159/000381893.
Results Reference
result
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=2751
Description
CICL670A2204 Results at Novartis Clinical Trials Results Website

Learn more about this trial

Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional Hemosiderosis

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