Overview

This trial is active, not recruiting.

Condition myelodysplastic syndromes
Treatments deferasirox, deferasirox placebo
Phase phase 2
Sponsor Novartis Pharmaceuticals
Start date March 2010
End date December 2017
Trial size 223 participants
Trial identifier NCT00940602, 2009-012418-38, CICL670A2302

Summary

The primary purpose of this study is to prospectively assess the efficacy and safety of iron chelation therapy with deferasirox compared to placebo in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Experimental)
At least 210 male or female patients, ≥ 18 years of age with low/int-1 MDS, as determined by IPSS score, who have serum ferritin >1000 mcg/L at screening. will be assigned to one of the two arms in a ratio of 2:1, deferasirox or matching placebo.
deferasirox ICL670, Exjade®
Deferasirox will be provided as 125 mg, 250 mg, and 500 mg dispersible tablets packaged in bulk high density polyethylene (HDPE) bottles with induction seals and child resistant closures.
(Placebo Comparator)
Matching placebo will be administered orally
deferasirox placebo Placebo
Placebo will be formulated and packaged to be indistinguishable from the 125 mg, 250 mg, and 500 mg tablets of deferasirox.

Primary Outcomes

Measure
To compare deferasirox to placebo with regard to event-free survival (a composite primary endpoint including death and non-fatal events related to cardiac and liver function) in low and int-1 risk MDS patient with transfusional iron overload.
time frame: From date of Randomization Up to 5 years1 year - 5 years

Secondary Outcomes

Measure
Hematologic improvement in terms of erythroid responses during treatment will be assessed
time frame: From date of Randomization Up to 5 years
Overall survival
time frame: From date of Randomization Up to 5 years
Proportion of patients with hypothyroidism
time frame: Annually
Proportion of patients with worsening of glucose metabolism
time frame: Annually
Disease progression
time frame: From date of Randomization Up to 5 years
Time to first occurrence of serum ferritin > 2 times the baseline value
time frame: From date of Randomization Up to 5 years
Time to at least a 10% increase from baseline in LVIDD
time frame: From date of Randomization Up to 5 years
Time to at least a 10% increase from baseline in LVISD
time frame: From date of Randomization Up to 5 years
Infections
time frame: From date of Randomization Up to 5 years
Proportion of patients with significant renal dysfunction
time frame: Annually
Proportion of patients with severe neutropenia or thrombocytopenia
time frame: Annually
Proportion of patients with major gastrointestinal bleeding
time frame: Annually
Time to study drug discontinuation due to an AE or laboratory abnormality
time frame: From date of Randomization Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Males or females ≥ 18 years of age - Patients must weigh between 35-135 kg MDS low -int-1 risk as determined by IPSS score and confirmed by bone marrow examination within 6 months prior to study entry - Ferritin> 1000 mcg/L at screening - History of 15 to 75 PRBC transfusions - Anticipated to be transfused at least 8 times annually during the study Exclusion Criteria: - More than 6 months of cumulative iron-chelation therapy (such as daily deferasirox (Exjade) or deferiprone or 5x/week deferosamine). intermittent deferoxamine doses in association with blood transfusions are not exclusionary regardless of duration of such treatment. -- More than 3 years since patient began receiving regular transfusions (2 units per 8 weeks or 4 units received in a 3 month period). - Creatinine clearance < 40 ml/min - Serum creatinine >1.5x ULN at screening - Significant proteinuria: urinary protein/creatinine ratio >0.5 mg/mg in a non first void urine sample - ECOG performance status > 2 - Left ventricular ejection fraction < 50% by ECHO - History of hospitalization for Congestive Heart Failure - Systemic disease that would prevent study treatment (uncontrolled hypertension, cardiovascular renal, hepatic (including Child-Pugh Class B and C) or metabolic disease) - Hepatitis B or C (HBsAg in the absences or HBsAB or HCV Ab positive with HCV RNA positive) - History of HIV positivity by (ELISA or Western blot) - Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start - ALT or AST > 3.5 x ULN at screening - Total bilirubin > 1.5 x ULN at screening - Diagnosis of liver cirrhosis - Patient participating in another clinical trial or receiving an investigational drug - History of another malignancy within the past five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ - History of non-compliance with medical regimen, or patients potentially unreliable and/or not cooperative - Presence of surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug - Pregnant or intending to become pregnant or breast-feeding patents - History of drug or alcohol abuse within the 12 months prior to enrollment. - Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

Official 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
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Novartis.
Location data was received from the National Cancer Institute and was last updated in September 2016.