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NCT00940602

Myelodysplastic Syndromes (MDS) Event Free Survival With Iron Chelation Therapy Study

Last Updated: 2020-11-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

225 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-22

Study Completion Date

2018-02-27

Brief Summary

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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.

Detailed Description

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This randomized, double blind trial to evaluate deferasirox vs placebo in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload consisted of four periods, a screening period, a treatment period, a post treatment follow-up period and a survival period. The trial recruitment period lasted until December 2014 and the trial continued for three years from the date the last patient enrolled until February 2018 (last patient last visit date).

Screening period:

The screening period lasting up to 35 days with two screening visits, at least 14 days apart, used to assess patient eligibility. Eligible patients with low or int-1 risk myelodysplastic syndromes (MDS) with transfusional iron overload were randomized in a 2:1 ratio to deferasirox or placebo respectively. Randomization was also stratified using the International prognostic scoring system of low or int-1 MDS and by geographical region (Asian vs non-Asian countries) since the Asian population has been reported to have a longer survival.

The following concomitant medications could be permitted for use while the patient was on study, and information outlining start date(s) and end date(s) of each medication taken were to be recorded on the appropriate eCRF: Erythropoietin (growth factor), G-CSF (growth factor), GM-CSF growth factor), Azacitidine, Thalidomide, Arsenic trioxide, Lenalidomide, Decitabine, Cyclosporine A, Vitamin C supplements (≤ 200 mg/day)

Treatment period:

The dosing schedule was 10 mg/kg/day (once daily) for the first 2 weeks, followed by 20 mg/kg/day (once daily). After 3 months of treatment at the dose of 20mg/kg/day, the dose could be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on the serum ferritin response. Placebo matching to each strength of the active deferasirox was utilized to maintain the double-blind trial design.

During the treatment period patients returned to the investigational site every four weeks for routine procedures and to monitor safety, efficacy and compliance to treatment.

An external Data Monitoring Committee (DMC) monitored patient safety and trial conduct and received a blinded summary of serious adverse events.

All suspected endpoint events were reviewed and adjudicated by the Endpoint Adjudication Committee (EAC) to ensure that all events that were reported were judged uniformly using the same criteria. The first confirmed suspected endpoint event for a patient was counted for the trial's composite primary endpoint, "event free survival". The composite primary endpoint, "event free survival," was defined for a patient as the date randomized to trial treatment to the date of the first documented non-fatal event, related to cardiac and liver function, transformation to AML, or death due to any cause.

When a patient had a non-fatal event, related to cardiac and liver function, and transformation to AML, the trial treatment (deferasirox or placebo) was discontinued. After trial treatment was discontinued, a 28 days post treatment safety assessment for AEs and SAEs was completed. Any patient who died during the treatment or 28 day post treatment safety assessment is represented in the all-cause mortality table in the safety section of this result. After trial treatment was discontinued for a patient, their treatment was un-blinded. Subsequent iron chelation treatment was subject to the patient's and investigator's decision. Patients continued to be followed during the post-treatment evaluation or survival follow up period, depending on their choice.

For patients who did not meet a non-fatal event, study treatment was continued as long as the patient and the treating physician felt it was in the best interest for the patient or until the trial terminated/completed. There was no un-blinding of the trial treatment for patients who terminated trial treatment without meeting a non-fatal event. Patients continued to be followed during the post-treatment evaluation or survival follow up period, depending on their choice.

A patient who discontinued study treatment without meeting a non-fatal component of the composite primary endpoint continued to be evaluated every 3 months. Once a patient stopped study evaluations they were followed for at least every 6 months for overall survival and any iron chelation therapies they are receiving up to the end of study.

Post-treatment evaluation period:

For patients who had a non-fatal event: After treatment termination, all patients were followed for safety (28 days) and then evaluated with visits every three months if they agreed to move into the post treatment evaluation phase.

For patients who did not meet a non-fatal event: After termination of study treatment, if a patient and investigator chose the post-treatment evaluation period, the patient was followed for safety and endpoints at visits occurring every three months.

Survival Follow Up period:

Subsequent to the post treatment evaluation period, or at the end of treatment period, if a patient and treating physician decided that the patient would not participate in the post treatment evaluation period, the patient was followed every 6 months for overall survival and iron chelation therapies.

The end of the study was defined as three years from the date the last patient was enrolled (last patient first visit).

The sample size of 210 patients did not provide sufficient power for testing statistical hypotheses. The statistical analysis was revised accordingly to concentrate on evaluating the treatment effect of deferasirox relative to placebo, and the study phase designation was changed from Phase lll to Phase II. Amendment 4 of the study adjusted the sample size, statistical analysis, and duration of the study and added two secondary endpoints: Hematologic improvement (HI) in terms of erythroid response and Frequency and rate of infections requiring intravenous (IV) antimicrobials. Upon approval of the amendment, patients signed a new consent form and continued the appropriate visit schedule.

Conditions

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Myelodysplastic Syndromes

Keywords

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TELESTO MDS Study Myelodysplastic Syndromes Myelodysplastic Syndromes (low-int-1 risk)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Patients, investigator staff, persons performing the assessments, and data analysts remained blind to the identity of the study treatment from the time of randomization until database lock.

Study Groups

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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.

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

Intervention Type DRUG

Other Intervention Names

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ICL670, Exjade®

Eligibility Criteria

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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

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

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Belgium Finland Netherlands Puerto Rico Romania Spain Sweden United States Australia Bulgaria Canada China Denmark Greece Hong Kong Italy Malaysia Mexico New Zealand Russia Switzerland Thailand United Kingdom

References

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Angelucci E, Li J, Greenberg P, Wu D, Hou M, Montano Figueroa EH, Rodriguez MG, Dong X, Ghosh J, Izquierdo M, Garcia-Manero G; TELESTO Study Investigators. Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial. Ann Intern Med. 2020 Apr 21;172(8):513-522. doi: 10.7326/M19-0916. Epub 2020 Mar 24.

Reference Type DERIVED

PMID: 32203980 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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2009-012418-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CICL670A2302

Identifier Type: -

Identifier Source: org_study_id

Myelodysplastic Syndromes (MDS) Event Free Survival With Iron Chelation Therapy Study

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Deferasirox

Deferasirox

Placebo

Placebo

Interventions

Deferasirox

Placebo

Other Intervention Names

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

Novartis Pharmaceuticals

Responsible Party

Principal Investigators

Novartis Pharmaceuticals

Locations

Pacific Cancer Medical Center, Inc. PAC Center

Rocky Mountain Cancer Centers RMCC

Willis-Knighton Cancer Center Dept of Onc

Henry Ford Hospital Henry Ford

Midwest Cancer Care Physicians MMCC

Mercy Medical Research Institute SC

Glacier View Research Institute - Cancer SC

Hackensack University Medical Center Department of Research

University of Texas MD Anderson Cancer Center Dept of MD Anderson (16)

Cancer Care Centers of South Texas HOAST CCC of So.TX- MedicalCenter(2)

Swedish Cancer Institute Ballard Campus

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