Myelodysplastic SyndromePhase 2NCT00110266
Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients
A Phase 2 study testing Deferasirox in people with Myelodysplastic Syndrome and Iron Overload, run by Novartis Pharmaceuticals at 48 sites in 2 countries.
Trial summary
The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Iron Overload
- What is being tested?
- Deferasirox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 48 sitesin 2 countries
- Study dates
- 25 Jul 2005to 28 Mar 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients with low or intermediate (INT-1) risk MDS
- Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).
- Age greater than or equal to 18 years
- Availability of transfusion records for the 12 weeks prior to registration
- A lifetime minimum of 30 previous packed red blood cell transfusions
- Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration
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- Serum Ferritin:
- For entry into the screening period, serum ferritin ≥ 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year.
- Serum ferritin ≥ 1000 ng/mL at screening via the central lab.
- Life expectancy ≥ 6 months
- Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)
- Able to provide written informed consent
Who cannot join
- Serum creatinine above the upper limit of normal
- Alanine aminotransferase (ALT) > 500 U/L during screening
- Clinical or laboratory evidence of active Hepatitis B or C
- Urinary protein/creatinine ratio > 0.5 mg/mg
- History of HIV positive test result (ELISA or Western blot)
- Eastern Cooperative Oncology Group (ECOG) Performance Status > 2
Show all 14Show fewer
- Patients with uncontrolled systemic hypertension
- Unstable cardiac disease not controlled by standard medical therapy
- Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation
- Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
- Pregnancy or breast feeding
- Treatment 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
- History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative
Trial locations and contacts
48 sites in 2 countries.
48 sites in 2 countries
United States42 sites
NMOHC
Albuquerque, New Mexico, 87109
Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital
Alexandria, Louisiana, 71301
Arlington Fairfax Hematology Oncology PC
Arlington, Virginia, 22205
Cancer Care of WNC
Asheville, North Carolina, 28801
Emory University School of Medicine/Winship Cancer Institute
Atlanta, Georgia, 30322
Rocky Mountain Cancer Centers
Aurora, Colorado, 80012
St. Agnes HealthCare
Baltimore, Maryland, 21231-1000
Univ of Alabama Birmingham
Birmingham, Alabama, 35294
Roswell Park Cancer Center
Buffalo, New York, 14623
Novartis Investigative Site
Chicago, Illinois, 60612
University of Chicago Hospital
Chicago, Illinois, 60637-1470
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
Bay Area Cancer Research Group
Concord, California, 94520
City of Hope National Medical Center
Duarte, California, 91010
The Cancer Center at Hackensack University
Hackensack, New Jersey, 07601
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
Baylor/The Methodist Hospital
Houston, Texas, 77030
Mayo Clinic
Jacksonville, Florida, 32224
University of Kansas Medical Center
Kansas City, Kansas, 66160
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0001
University of Kentucky College of Medicine, Markey Cancer Center
Lexington, Kentucky, 40536-0093
Cedars-Sinai Medical Center, UCLA School of Medicine
Los Angeles, California, 90048
UCLA Medical Center
Los Angeles, California, 90095-1678
The West Cancer Clinic
Memphis, Tennessee, 38120
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Novartis Investigative site
Nashville, Tennessee, 37232
Oncology Hematology West, PC
Omaha, Nebraska, 68124-2346
Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Phoenix, Arizona, 85054
Western Pennsylvania Hospital Cancer Institute
Pittsburgh, Pennsylvania, 15224
Novartis Investigative Site
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
Rochester General Hospital/Lipson Cancer and Blood Center
Rochester, New York, 14621
Utah Cancer Specialists
Salt Lake City, Utah, 84106
UCSF
San Francisco, California, 94143-0324
UCSF
San Francisco, California, 94143
Novartis Investigative Site
Southfield, Michigan, 48075
Novartis Investigative Site
Spokane, Washington, 99202
The Center for Cancer Care & Research (TCCCR)
St Louis, Missouri, 63110
Wake Forest UniversitComprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1082
Rush Cancer Institute Univ. of Massachussets Medical Center
Worcester, Massachusetts, 01605
Canada6 sites
Novartis Investigative Site
Hamilton, Ontario, L8N 3Z5
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, H2L 4M1
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, M5g 2M9
Novartis Investigative Site
Vancouver, British Columbia, V6Z 1Y6
About this study
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 Using Serum Ferritin Monitoring
The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.
Read the detailed description
Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.
- Conditions
- Myelodysplastic Syndrome, Iron Overload
- Being tested
- Deferasirox
- Keywords
- ICL670, Deferasirox, Iron chelation, Chelator, Desferal
- Medical subject headings
- Myelodysplastic Syndromes, Iron Overload
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferasiroxDrug
Also called ICL670A, chelator, desferal, iron chelation
20 mg/kg/day over one year in patients with MDS
| Study group | Role | What they receive |
|---|---|---|
| ICL670 | Experimental | Evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS Receives: Drug: Deferasirox |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting Adverse Events
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.
Measured: up to 53 Weeks
Secondary outcomes (11)
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).
Measured: From Baseline to Weeks 13, 25, 37 and 53
Change in Labile Plasma Iron (LPI)
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
Measured: From Baseline to Weeks 13, 25, 37 and 49
Directly Chelatable Iron (DCI)
The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.
Measured: From Baseline to Weeks 13, 25, 37 and 49
Total Iron Levels
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.
Measured: From Baseline to Weeks 13, 25, 37, 49 and 53
Serum Transferrin Levels
Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.
Measured: From Baseline to Weeks 13, 25, 37, 49 and 53
Transferrin Saturation
Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.
Measured: From Baseline to Weeks 13, 25, 37, 49 and 53
Transfusion Requirements
Number of participants receiving transfusions, the summarized during the study.
Measured: up to 1 year
Frequency of Hematologic Improvement During the Study
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.
Measured: up to 1 year
Trough Plasma Deferasirox Concentration
The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.
Measured: At Week 13, 25, 37 and 49
Treatment Compliance to Deferasirox
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.
Measured: up to 1 year
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
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.
Measured: up to Week 13 (Month 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2005 (estimated)
- Study start25 Jul 2005
- Primary completion28 Mar 2008
- Study completion28 Mar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110266
- Sponsor's protocol ID
- CICL670AUS03
- Status last verified
- Jul 2021
- First submitted
- 4 May 2005
- Last updated
- 16 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012 Jun 10;30(17):2134-9. doi: 10.1200/JCO.2010.34.1222. Epub 2012 Apr 30.
PubMed 22547607
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Using Serum Ferritin Monitoring
- ClinicalTrials.gov ID
- NCT00110266
- Acronym / sponsor ID
- CICL670AUS03
- Conditions
- Myelodysplastic Syndrome, Iron Overload
- Keywords
- ICL670, Deferasirox, Iron chelation, Chelator, Desferal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Jul 2005 (actual)
- Primary completion
- 28 Mar 2008 (actual)
- Study completion
- 28 Mar 2008 (actual)
- First posted
- 5 May 2005 (estimated)
- Results
- Posted 16 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.
Detailed description
Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ICL670 | Experimental | Drug: DeferasiroxEvaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female patients with low or intermediate (INT-1) risk MDS
- Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).
- Age greater than or equal to 18 years
- Availability of transfusion records for the 12 weeks prior to registration
- A lifetime minimum of 30 previous packed red blood cell transfusions
Key exclusion criteria (14 listed)
- Serum creatinine above the upper limit of normal
- Alanine aminotransferase (ALT) > 500 U/L during screening
- Clinical or laboratory evidence of active Hepatitis B or C
- Urinary protein/creatinine ratio > 0.5 mg/mg
- History of HIV positive test result (ELISA or Western blot)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferasiroxAlso: ICL670A, chelator, desferal, iron chelation20 mg/kg/day over one year in patients with MDS | Drug | ICL670 |
Primary outcome
Number of Participants Reporting Adverse Events
Time frame: up to 53 Weeks
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.
11 secondary outcomes
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
Time frame: From Baseline to Weeks 13, 25, 37 and 53
Change in Labile Plasma Iron (LPI)
Time frame: From Baseline to Weeks 13, 25, 37 and 49
Directly Chelatable Iron (DCI)
Time frame: From Baseline to Weeks 13, 25, 37 and 49
Total Iron Levels
Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Serum Transferrin Levels
Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Transferrin Saturation
Time frame: From Baseline to Weeks 13, 25, 37, 49 and 53
Transfusion Requirements
Time frame: up to 1 year
Frequency of Hematologic Improvement During the Study
Time frame: up to 1 year
Trough Plasma Deferasirox Concentration
Time frame: At Week 13, 25, 37 and 49
Treatment Compliance to Deferasirox
Time frame: up to 1 year
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
Time frame: up to Week 13 (Month 3)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22547607List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012 Jun 10;30(17):2134-9. doi: 10.1200/JCO.2010.34.1222. Epub 2012 Apr 30.
- Results for CICL670AUS03 from the Novartis Clinical Trials websiteLink provided by the sponsor.
- Publication (Embasse # 2012421150)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
48 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Deferasirox in people with Myelodysplastic Syndrome and Iron Overload, run by Novartis Pharmaceuticals at 48 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Reporting Adverse Events (time frame: up to 53 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00110266, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2021.