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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
15/07/2009
Date last updated
14/12/2018

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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

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 is defined as the time from date of randomization to date of death or any of the non-fatal events as specified in the protocol.
Timepoint [1] 0 0
Time to event (Up to Year 5)
Secondary outcome [1] 0 0
Proportion of patients with hematologic improvement in terms of erythroid response - Improvement is defined as a hemoglobin increase of = 1.5 g/dL, or a reduction of = 4 RBC transfusions/8 weeks in comparison to pre-treatment values and lasting at least 8 weeks. This outcome measure was pre-specified for patients with pre-treatment hemoglobin levels of less than 11 g/dL or RBC transfusion dependence.
Timepoint [1] 0 0
Baseline up to Year 5
Secondary outcome [2] 0 0
Overall survival (days) - Overall survival was calculated as the date of death (irrespective of cause) minus date of randomization plus 1.
Timepoint [2] 0 0
Time to event (Up to Year 5)
Secondary outcome [3] 0 0
Proportion of patients with hypothyroidism - As assessed by annual measurement of TSH and free T4. Hypothyroidism is defned as follows:
primary hypothyroidism: serum TSH >ULN and free T4 <LLN;
secondary hypothyroidism: serum TSH <ULN and free T4 <LLN;
subclinical hypothyroidism: TSH >ULN and a free T4 within normal limits.
Timepoint [3] 0 0
Up to Year 5
Secondary outcome [4] 0 0
Proportion of patients with worsening of glucose metabolism - An annual oral glucose tolerance test (OGTT) was carried out. The proportion of patients with 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 their baseline result was determined. Fasting and 2-hour post-prandial plasma glucose levels were measured.
Timepoint [4] 0 0
Baseline up to Year 5
Secondary outcome [5] 0 0
Time to disease progression - An evaluation of the time from randomization to either MDS progression or progression to AML in the treatment groups will be done based on date of diagnosis of MDS progression or date of first diagnosis of AML minus date of randomization plus 1. MDS progression will be defined as a transition into a higher MDS risk group based on IPSS scoring. Progression to AML will be defined based upon the most current classification guidelines (Vardiman 2009), as 20% or more blasts seen in the bone marrow.
Timepoint [5] 0 0
Time to event (Baseline up to Year 5)
Secondary outcome [6] 0 0
Time to first occurrence of serum ferritin > 2 times the baseline value - An evaluation of the time from randomization to the first occurrence of serum ferritin > 2 times the baseline value at two consecutive assessments (at least two weeks apart) will be performed per treatment group based on the following variable: • date of the first of the two consecutive laboratory assessment fulfilling the criterion of SF > 2 × baseline value minus date of randomization plus 1.
Timepoint [6] 0 0
Time to event (Baseline up to Year 5)
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 - An evaluation of the time from randomization to the first occurrence of an increase of at least 10% from the baseline value of LVIDD will be performed based on the following variable: • date of echocardiography assessment where a minimum of 10% increase first occurred minus date of randomization plus 1.
Timepoint [7] 0 0
Time to event (Baseline up to Year 5)
Secondary outcome [8] 0 0
Time to at least a 10% increase from baseline in LVISD - An evaluation of the time from randomization to the first occurrence of an increase of at least 10% from the baseline value of LVISD will be performed based on the following variable:
• date of echocardiography assessment where a minimum of 10% increase first occurred minus date of randomization plus 1.
Timepoint [8] 0 0
Time to event (Baseline up to Year 5)
Secondary outcome [9] 0 0
Rate of infections requiring intravenous antimicrobials - Infections were determined from the reported adverse events with system organ class "Infections and infestations" and action taken "Concomitant medication taken." One patient could contribute more than one infection event. To account for different lengths of observation time in the two groups, the rate of infections was calculated based on patient-years of follow-up.
Timepoint [9] 0 0
Up to Year 5
Secondary outcome [10] 0 0
Proportion of patients with significant renal dysfunction - Significant renal dysfunction is defined as a serum creatinine value = 2 times ULN at two consecutive assessments at least 7 days apart.
Timepoint [10] 0 0
Up to Year 5
Secondary outcome [11] 0 0
Proportion of patients with severe neutropenia or thrombocytopenia - Proportion of patients with newly occurring CTCAE grade 4 neutropenia or thrombocytopenia will be displayed by treatment group. Results will also be provided for annual time intervals.
Timepoint [11] 0 0
Up to Year 5
Secondary outcome [12] 0 0
Proportion of patients with major gastrointestinal bleeding - Major gastrointestinal bleeding is defined as an AE that may include one of the following MedDRA preferred terms: gastric haemorrhage; gastrointestinal haemorrhage; small intestinal haemorrhage; oesophageal haemorrhage; large intestinal haemorrhage; rectal haemorrhage; melaena; duodenal ulcer haemorrhage; gastric ulcer haemorrhage; peptic ulcer haemorrhage; large intestinal ulcer haemorrhage; oesophageal ulcer haemorrhage; haematochezia
Timepoint [12] 0 0
Up to Year 5
Secondary outcome [13] 0 0
Time to study drug discontinuation due to an AE or laboratory abnormality - Calculated as the date of study drug discontinuation due to an AE or laboratory abnormality minus the date of randomization plus 1.
Timepoint [13] 0 0
Time to event (Up to Year 5)

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
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Montana
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Plovdiv
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sofia
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Varna
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Manitoba
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Guangdong
Country [20] 0 0
China
State/province [20] 0 0
Hubei
Country [21] 0 0
China
State/province [21] 0 0
Jiangsu
Country [22] 0 0
China
State/province [22] 0 0
Shanghai
Country [23] 0 0
China
State/province [23] 0 0
Sichuan
Country [24] 0 0
China
State/province [24] 0 0
Tianjin
Country [25] 0 0
China
State/province [25] 0 0
Zhejiang
Country [26] 0 0
China
State/province [26] 0 0
Beijing
Country [27] 0 0
China
State/province [27] 0 0
Jinan
Country [28] 0 0
Denmark
State/province [28] 0 0
Copenhagen
Country [29] 0 0
Denmark
State/province [29] 0 0
Herlev
Country [30] 0 0
Greece
State/province [30] 0 0
GR
Country [31] 0 0
Greece
State/province [31] 0 0
Athens
Country [32] 0 0
Hong Kong
State/province [32] 0 0
Hong Kong
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Shatin, New Territories
Country [34] 0 0
Italy
State/province [34] 0 0
BO
Country [35] 0 0
Italy
State/province [35] 0 0
CA
Country [36] 0 0
Italy
State/province [36] 0 0
CT
Country [37] 0 0
Italy
State/province [37] 0 0
FG
Country [38] 0 0
Italy
State/province [38] 0 0
FI
Country [39] 0 0
Italy
State/province [39] 0 0
ME
Country [40] 0 0
Italy
State/province [40] 0 0
PE
Country [41] 0 0
Italy
State/province [41] 0 0
RC
Country [42] 0 0
Italy
State/province [42] 0 0
RM
Country [43] 0 0
Italy
State/province [43] 0 0
TO
Country [44] 0 0
Italy
State/province [44] 0 0
Napoli
Country [45] 0 0
Malaysia
State/province [45] 0 0
Sarawak
Country [46] 0 0
Malaysia
State/province [46] 0 0
Selangor
Country [47] 0 0
Mexico
State/province [47] 0 0
Distrito Federal
Country [48] 0 0
New Zealand
State/province [48] 0 0
Auckland 6
Country [49] 0 0
New Zealand
State/province [49] 0 0
Auckland
Country [50] 0 0
New Zealand
State/province [50] 0 0
Christchurch
Country [51] 0 0
Romania
State/province [51] 0 0
Jud Mures
Country [52] 0 0
Romania
State/province [52] 0 0
Bucharest
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Moscow
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Rostov on Don
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Saint Petersburg
Country [56] 0 0
Switzerland
State/province [56] 0 0
Basel
Country [57] 0 0
Switzerland
State/province [57] 0 0
Zurich
Country [58] 0 0
Thailand
State/province [58] 0 0
THA
Country [59] 0 0
Thailand
State/province [59] 0 0
Bangkok
Country [60] 0 0
Thailand
State/province [60] 0 0
Chiang Mai
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Scotland
Country [62] 0 0
United Kingdom
State/province [62] 0 0
West Yorkshire
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Birmingham
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Bournemouth
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Cardiff
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Exeter
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Kent
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Macclesfield
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Nottingham
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to evaluate deferasirox and placebo with regard to event-free
survival (EFS) (a composite primary endpoint including death and non-fatal events related to
cardiac and liver function and transformation to AML) in patients with myelodysplastic
syndromes (low/int-1 risk) and transfusional iron overload.
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