A multi-center, randomized, double-blind, placebo-controlled clinical trial of deferasirox in patients with myelodysplastic syndromes (low/int-1risk) and transfusional iron overload (TELESTO)
The goal of this clinical research study is to study the effectiveness of the drug Exjade® (deferasirox) in controlling MDS. Researchers will also study the effect of the study drug/placebo on the heart, kidneys, and liver.
Disease Group: Leukemia
Treatment Agent: Deferasirox
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Novartis Pharmaceuticals
The purpose of this study is to evaluate in low/int-1 risk MDS patients, treated as per standard practice, the clinical benefit of deferasirox versus placebo, while rigorously monitoring relevant clinical parameters (cardiac and liver function and transformation to AML) potentially affected by iron overload complications. The primary objective is 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 patients with transfusional iron overload. Primary objective The primary objective is to evaluate deferasirox and placebo with regard to event-free survival (a composite primary endpoint including death and non-fatal events related to cardiac and liver function and transformation to AML) in low and int-1 risk MDS patients with transfusional iron overload. The secondary objectives are to evaluate: Hematologic improvement (HI) in terms of erythroid response Overall survival Change in endocrine function (thyroid and glycemic control) Disease progression (which includes MDS progression and progression to AML) Change in serum ferritin level Change in cardiac function Frequency of infections requiring intravenous antimicrobials Safety, in particular to assess the levels of increased risk for pre-specified adverse events (renal dysfunction, neutropenia, thrombocytopenia, gastrointestinal bleeding, and laboratory abnormalities) that would be clinically unacceptable in the context of the level of benefit that is likely to be provided by iron chelation using deferasirox in MDS patients with iron overload
IRB Review and Approval Date: 09/02/2010
Recruitment Status: Closed
Projected Accrual: 210
1) Male or female patients, greater than or equal to 18 years of age.
2) Patient must weigh between 35-135 kg
3) Patients with low or intermediate (int-1) risk MDS, as determined by IPSS score. This must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable.
4) Ferritin > 1000 mcg/L and at screening. Serum ferritin will be measured at Screening Visit 1 and Screening Visit 2 (at least 14 days apart) and the mean value will be used for eligibility criteria.
5) History of transfusion of 15 to 75 PRBC units.
6) Anticipated to be transfused with at least 8 units of PRBC annually during the study.
7) Women of child-bearing potential using effective methods of contraception during dosing of study treatment.
1) More than 3 years since patient began receiving regular transfusions
(2 units per 8 weeks or 4 units received in a 3 month period).
2) Creatinine Clearance <40 ml/min
3) Serum creatinine > 1.5 x ULN at screening
4) Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample at Visit 1 or Visit 2 (or alternatively in two of three samples obtained for screening).
5) ECOG performance status > 2.
6) Left ventricular ejection fraction < 50% by echocardiography as per the central reading assessment.
7) A history of hospitalization for congestive heart failure.
8) Systemic diseases which would prevent study treatment (e.g.uncontrolled hypertension, cardiovascular, renal, hepatic [including Child-Pugh Class B and C], metabolic, etc.).
9) Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive).
10) History of HIV positive test result (ELISA or Western blot).
11) Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start.
12) ALT or AST > 3.5 × ULN at screening.
13) Total bilirubin > 1.5 x ULN at screening.
14) Diagnosis of liver cirrhosis (either established diagnosis or diagnosis by liver biopsy or central ultrasound reading).
15) Patients participating in another clinical trial other than an observational registry study.
16) Patients with a 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.
17) History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative.
18) Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug.
19) Pregnant, or breast-feeding patients, or patients of childbearing potential not employing an effective method of birth control.
20) History of drug or alcohol abuse within the 12 months prior to enrollment.
21) More than 6 months of cumulative iron chelation therapy (such as daily deferasirox (Exjade) or deferiprone or 5x/week deferoxamine
22) Intermittent deferoxamine doses in association with blood transfusions are not exclusionary regardless of duration of such treatment.