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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00940602




Registration number
NCT00940602
Ethics application status
Date submitted
15/07/2009
Date registered
16/07/2009
Date last updated
23/11/2020

Titles & IDs
Public title
Myelodysplastic Syndromes (MDS) Event Free Survival With Iron Chelation Therapy Study
Scientific title
A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of Deferasirox in Patients With Myelodysplastic Syndromes (Low/Int-1 Risk) and Transfusional Iron Overload
Secondary ID [1] 0 0
2009-012418-38
Secondary ID [2] 0 0
CICL670A2302
Universal Trial Number (UTN)
Trial acronym
TELESTO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Deferasirox
Treatment: Drugs - Placebo

Experimental: Deferasirox - 10 mg/kg/day (once daily) for the first 2 weeks of treatment, followed by 20 mg/kg/day (once daily) from Week 2 to End of Treatment. After 3 months of treatment at 20 mg/kg/day, the dose was allowed to be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on serum ferritin responses. When a target serum ferritin level was reached (usually between 500 and 1000 µg/L), the dose could be reduced by 50% to maintain the serum ferritin within the target range.

Placebo Comparator: Placebo - 10 mg/kg/day (once daily) for the first 2 weeks of treatment, followed by 20 mg/kg/day (once daily) from Week 2 to End of Treatment. After 3 months of treatment at 20 mg/kg/day, the dose was allowed to be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on serum ferritin responses. When a target serum ferritin level was reached (usually between 500 and 1000 µg/L), the dose could be reduced by 50% to maintain the serum ferritin within the target range.


Treatment: Drugs: Deferasirox
Deferasirox provided as 125 mg, 250 mg, and 500 mg dispersible tablets for oral use

Treatment: Drugs: Placebo
Inactive ingredients used as a placebo comparator, provided as 125 mg, 250 mg, and 500 mg dispersible tablets for oral use

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival - Event-free survival was defined as the time from the date of randomization to the date of the first documented non-fatal event (worsening cardiac function, hospitalization for congestive heart failure, liver function impairment, liver cirrhosis, transformation to AML, as defined in the protocol), or death, whichever occurred first. Participants who did not experience a non-fatal event as of the time of data cut-off (end of study), as well as participants who did not experience a non-fatal event and stopped study participation before the data cut-off, were censored as specified in the protocol.
Timepoint [1] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [1] 0 0
Percentage of Participants With Hematologic Improvement (HI) in Terms of Erythroid Response - HI in terms of erythroid responses was assessed based on International Working Group (IWG) criteria, with improvement defined as follows:
Hemoglobin increase of = 1.5 g/dL OR
Reduction of = 4 RBC transfusions/8 weeks in comparison to pre-treatment values and lasting at least 8 weeks. The last hemoglobin value measured prior to randomization was used as the pre-treatment value. The last available lab assessment date was used as the cut-off date for the analysis.
Timepoint [1] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [2] 0 0
Overall Survival - Overall survival was calculated as the date of death (irrespective of cause) minus date of randomization plus 1.
Timepoint [2] 0 0
Day 1 to end of treatment period, approx. 7.4 years
Secondary outcome [3] 0 0
Percentage of Participants With Newly Occurring Hypothyroidism Compared to Baseline - As assessed by annual measurement of Thyroid Stimulating Hormone (TSH) and free T4. Hypothyroidism was defined as follows and is inclusive of:
Primary hypothyroidism: serum TSH >upper limit of normal (ULN) and free T4 <lower limit of normal (LLN);
Secondary hypothyroidism: serum TSH <ULN and free T4 <lower limit of normal;
Subclinical hypothyroidism: TSH >ULN and a free T4 within normal limits. The last available lab assessment date was used as the cut-off date for the analysis.
Timepoint [3] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [4] 0 0
Percentage of Participants With Worsening Glucose Metabolism Compared to Baseline - As assessed by an annual glucose tolerance test (OGTT). Worsening glucose metabolism was defined as an increase in glucose metabolism category (normal, impaired glucose metabolism, diabetes mellitus) based on the American Diabetes Association criteria (American Diabetes Association 2009) compared to the baseline result. The last available lab assessment date was used as the cut-off date for the analysis.
Timepoint [4] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [5] 0 0
Time to Disease Progression - Disease progression was defined as follows:
MDS progression: Transition into a higher MDS risk group based on IPSS scoring
Progression to AML: 20 percent or more blasts seen in the bone marrow collected by biopsy or aspirate.
Disease progression was calculated as follows: Date of diagnosis of MDS progression or date of first diagnosis of AML, minus date of randomization plus 1. Participants who neither experienced MDS progression nor progression to AML were censored at the last contact date.
Timepoint [5] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [6] 0 0
Time to First Occurrence of Serum Ferritin Level >2 Times the Baseline Value at Two Consecutive Assessments (at Least Two Weeks Apart) - Assessed by blood draw and calculated as follows: Date of first occurrence of serum ferritin >2 times the baseline value at two consecutive assessments (at least two weeks apart), minus date of randomization plus 1. Participants who did not experience such an increase were censored at the last date when serum ferritin was available.
Timepoint [6] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [7] 0 0
Time to at Least a 10% Increase From Baseline in Left Ventricular End-diastolic Internal (LVIDD) at Two Consecutive Assessments at Least Two Weeks Apart - Assessed by echocardiography and calculated as follows: Date of echocardiography assessment where a minimum of 10% increase of LVIDD first occurred, minus date of randomization plus 1. Participants who did not experience such an increase were censored at the last date when LVIDD was available.
Timepoint [7] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [8] 0 0
Time to at Least a 10% Increase From Baseline in Left Ventricular Internal Systolic Diameter (LVISD) at Two Consecutive Assessments at Least Two Weeks Apart - Assessed by echocardiography and calculated as follows: Date of echocardiography assessment where a minimum of 10% increase of LVISD first occurred, minus date of randomization plus 1. Participants who did not experience such an increase were censored at the last date when LVISD was available.
Timepoint [8] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [9] 0 0
Total Number of Infections Requiring Intravenous Antimicrobials - The total number of infections were counted and summarized per treatment group. For this number, one participant can contribute more than one infection event. Infections were determined from the reported AEs with system organ class "Infections and infestations" and action taken "Concomitant medication taken." Antimicrobial therapy was determined from the reported concomitant medications for participants who had an infection AE. The route of administration needed to be specified as "intravenous (i.v.)". End of treatment period was defined as the treatment period plus 28 days.
Timepoint [9] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [10] 0 0
Percentage of Participants With Major Gastrointestinal Bleeding - Major gastrointestinal bleeding was defined as an AE that could include one of the following MedDRA preferred terms: gastric hemorrhage, gastrointestinal hemorrhage, small intestinal hemorrhage, esophageal hemorrhage, large intestinal hemorrhage, rectal hemorrhage, melaena, duodenal ulcer hemorrhage, gastric ulcer hemorrhage, peptic ulcer hemorrhage, large intestinal ulcer hemorrhage, esophageal ulcer hemorrhage, and hematochezia. The end of treatment period was defined as the treatment period plus 28 days.
Timepoint [10] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [11] 0 0
Percentage of Participants With Significant Renal Dysfunction - Significant renal dysfunction was defined as a serum creatinine value = 2 times upper limit of normal (ULN) at two consecutive assessments at least 7 days apart
Timepoint [11] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [12] 0 0
Percentage of Participants With Newly Occurring Moderate or Severe Neutropenia - Moderate or severe neutropenia was defined as neutrophil counts less than 1.0×10E9/L.
Timepoint [12] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [13] 0 0
Percentage of Participants With Newly Occurring Severe Thrombocytopenia - Severe thrombocytopenia was defined as platelets counts less than 50×10E9/L.
Timepoint [13] 0 0
Day 1 to end of treatment period, approx. 7 years
Secondary outcome [14] 0 0
Time to Study Drug Discontinuation Due to an AE or Laboratory Abnormality - As recorded on the Study Treatment Completion electronic Case Report Form (eCRF), date and reason given.Only participants for whom the reason for stopping study medication was entered as AE or laboratory abnormality were considered. This time to event endpoint was calculated as the date of study drug discontinuation due to an AE or laboratory abnormality minus date of randomization plus 1. Participants who did not discontinue study medication due to an AE or laboratory abnormality were censored at the date of study drug discontinuation.
Timepoint [14] 0 0
Day 1 to end of treatment period, approx. 7 years

Eligibility
Key inclusion criteria
- Weigh between 35-135 kilograms

- Low or int-1 risk MDS

- Ferritin >1000 micrograms/liter at screening

- History of transfusion of 15 to 75 Packed Red Blood Cells (PRBC) units

- Anticipated to be transfused with at least 8 units of PRBCs annually during the study

- Women of child-bearing potential using effective methods of contraception during
dosing of study treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- More than 6 months of cumulative ICT (such as daily deferasirox (Exjade®) or
deferiprone or 5×/week deferoxamine)

- More than 3 years since patient began receiving regular transfusions (2 units per 8
weeks or 4 units received in a 3 month period)

- Significant proteinuria

- History of hospitalization for congestive heart failure; other heart conditions as
specified in the protocol

- Systemic diseases which would prevent study treatment

- Hepatitis B; Hepatitis C; HIV

- Liver cirrhosis

- Pregnant, or breast-feeding patients, or patients of child-bearing potential not
employing an effective method of birth control

- History of drug or alcohol abuse within the 12 months prior to enrollment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Montana
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Bulgaria
State/province [10] 0 0
Plovdiv
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Sofia
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Varna
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Manitoba
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
China
State/province [17] 0 0
Guangdong
Country [18] 0 0
China
State/province [18] 0 0
Hubei
Country [19] 0 0
China
State/province [19] 0 0
Jiangsu
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Tianjin
Country [22] 0 0
China
State/province [22] 0 0
Zhejiang
Country [23] 0 0
China
State/province [23] 0 0
Beijing
Country [24] 0 0
China
State/province [24] 0 0
Jinan
Country [25] 0 0
Denmark
State/province [25] 0 0
Copenhagen
Country [26] 0 0
Denmark
State/province [26] 0 0
Herlev
Country [27] 0 0
Greece
State/province [27] 0 0
GR
Country [28] 0 0
Greece
State/province [28] 0 0
Athens
Country [29] 0 0
Greece
State/province [29] 0 0
Patras
Country [30] 0 0
Hong Kong
State/province [30] 0 0
Hong Kong
Country [31] 0 0
Hong Kong
State/province [31] 0 0
Shatin, New Territories
Country [32] 0 0
Italy
State/province [32] 0 0
BO
Country [33] 0 0
Italy
State/province [33] 0 0
CA
Country [34] 0 0
Italy
State/province [34] 0 0
FG
Country [35] 0 0
Italy
State/province [35] 0 0
FI
Country [36] 0 0
Italy
State/province [36] 0 0
ME
Country [37] 0 0
Italy
State/province [37] 0 0
PE
Country [38] 0 0
Italy
State/province [38] 0 0
RC
Country [39] 0 0
Italy
State/province [39] 0 0
TO
Country [40] 0 0
Malaysia
State/province [40] 0 0
Sarawak
Country [41] 0 0
Malaysia
State/province [41] 0 0
Selangor
Country [42] 0 0
Mexico
State/province [42] 0 0
Distrito Federal
Country [43] 0 0
New Zealand
State/province [43] 0 0
Auckland 6
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Christchurch
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Moscow
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Rostov on Don
Country [48] 0 0
Switzerland
State/province [48] 0 0
Basel
Country [49] 0 0
Switzerland
State/province [49] 0 0
Zurich
Country [50] 0 0
Thailand
State/province [50] 0 0
THA
Country [51] 0 0
Thailand
State/province [51] 0 0
Bangkok
Country [52] 0 0
Thailand
State/province [52] 0 0
Chiang Mai
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Scotland
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Birmingham
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Bournemouth
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Cardiff
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Exeter
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Kent
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Macclesfield
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Nottingham
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This was a randomized, double-blind trial to evaluate deferasirox vs placebo in patients with
myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload .The trial was
conducted in 17 countries, started in 2010 and ended in 2018.
Trial website
https://clinicaltrials.gov/show/NCT00940602
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications