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Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

Primary Purpose

Myelodysplastic Syndromes, Iron Overload

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Deferasirox
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring MDS, Myelodysplastic Syndrome, ICL-670, ICL-670 and Myelodysplastic Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Stanford University Medical Center
  • Karmanos Cancer Center
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deferasirox

Arm Description

Participants received deferasirox 20mg/kg/day OD for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Absolute Change in Serum Ferritin From Baseline to Week 52
Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670).
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).
To Evaluate Change in Transfusion Requirements
Change in transfusion requirements from baseline.
Absolute Change in Serum Erythropoietin
Absolute Change in Serum Erythropoietin from baseline.
Absolute Change in Urinary Hepcidin
Absolute Change in Urinary Hepcidin from baseline
Absolute Change in Transferrin Saturation
Transferrin Saturation was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2)
Labile Plasma Iron (LPI)
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.

Full Information

First Posted
June 30, 2005
Last Updated
June 1, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00117507
Brief Title
Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients
Official Title
An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-Risk and INT-1 Myelodysplastic Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
January 2008 (Actual)
Study Completion Date
January 2008 (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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Iron Overload
Keywords
MDS, Myelodysplastic Syndrome, ICL-670, ICL-670 and Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
Participants received deferasirox 20mg/kg/day OD for 12 months. Deferasirox was taken every morning 30 minutes before breakfast, if possible consistently around the same time between 7:00 and 9:00 AM. The tablets was dropped into water or orange juice and gently stirred for 1 to 3 minutes until completely dispersed.
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Other Intervention Name(s)
Chelator, Iron chelator
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events and Serious Adverse Events
Description
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
Secondary Outcome Measure Information:
Title
Absolute Change in Serum Ferritin From Baseline to Week 52
Description
Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670).
Time Frame
Baseline to Week 52
Title
Absolute Change in Liver Iron Concentration (LIC) From Baseline to End of Study
Description
LIC was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2).
Time Frame
Baseline to Week 52
Title
To Evaluate Change in Transfusion Requirements
Description
Change in transfusion requirements from baseline.
Time Frame
Baseline to Week 52
Title
Absolute Change in Serum Erythropoietin
Description
Absolute Change in Serum Erythropoietin from baseline.
Time Frame
Baseline to Week 52
Title
Absolute Change in Urinary Hepcidin
Description
Absolute Change in Urinary Hepcidin from baseline
Time Frame
Baseline to Week 52
Title
Absolute Change in Transferrin Saturation
Description
Transferrin Saturation was assessed using magnetic resonance imaging (MRI) mean liver proton transverse relaxation rates (R2)
Time Frame
Baseline to Week 52
Title
Labile Plasma Iron (LPI)
Description
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.
Time Frame
Baseline to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305-5821
Country
United States
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20615548
Citation
Greenberg PL, Koller CA, Cabantchik ZI, Warsi G, Glynos T, Paley C, Schiffer C. Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes. Leuk Res. 2010 Dec;34(12):1560-5. doi: 10.1016/j.leukres.2010.06.013. Epub 2010 Jul 8.
Results Reference
background
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=2751
Description
Results for CICL670AUS02 from the Novartis Clinical Trials website

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Study for the Treatment of Transfusional Iron Overload in Myelodysplastic Patients

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