Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients
- Registration Number
- NCT00110266
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this trial is to examine the safety and efficacy of deferasirox in patients with Myelodysplastic Syndrome (MDS) and chronic iron overload from blood transfusions.
- Detailed Description
Study entry requires a diagnosis of low or intermediate (INT-1) risk MDS per International Prognostic Scoring System (IPSS) criteria and serum ferritin ≥ 1000 ng/mL. Patients must have had at least 30 prior red blood cell transfusions. Deferasirox will be administered at an initial dose of 20 mg/kg orally once per day. Patient transfusion history and at least three complete blood count (CBC) values must be available for the 12 weeks prior to study registration for patients with MDS and chronic iron overload from blood transfusions.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 176
- Male or female patients with low or intermediate (INT-1) risk MDS
- Patients can be EITHER naïve to iron chelation OR have had prior treatment with deferoxamine (DFO).
- Age greater than or equal to 18 years
- Availability of transfusion records for the 12 weeks prior to registration
- A lifetime minimum of 30 previous packed red blood cell transfusions
- Availability of at least three CBC values (pretransfusion) during the 12 weeks prior to registration
- Serum Ferritin:
For entry into the screening period, serum ferritin ≥ 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year.
Serum ferritin ≥ 1000 ng/mL at screening via the central lab.
- Life expectancy ≥ 6 months
- Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)
- Able to provide written informed consent
- Serum creatinine above the upper limit of normal
- Alanine aminotransferase (ALT) > 500 U/L during screening
- Clinical or laboratory evidence of active Hepatitis B or C
- Urinary protein/creatinine ratio > 0.5 mg/mg
- History of HIV positive test result (ELISA or Western blot)
- Eastern Cooperative Oncology Group (ECOG) Performance Status > 2
- Patients with uncontrolled systemic hypertension
- Unstable cardiac disease not controlled by standard medical therapy
- Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation
- Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
- Pregnancy or breast feeding
- Treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days
- Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug
- History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ICL670 Deferasirox Evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS
- Primary Outcome Measures
Name Time Method Number of Participants Reporting Adverse Events up to 53 Weeks Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
- Secondary Outcome Measures
Name Time Method Change in Labile Plasma Iron (LPI) From Baseline to Weeks 13, 25, 37 and 49 LPI represents the component of non-transferrin bound iron and is an indicator of iron overload. The blood sample for LPI determinations was collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49. LPI was calculated as 1 LPI unit = the quantity of reactive oxygen species produced by approximately 1.5 μM Fe
Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53 From Baseline to Weeks 13, 25, 37 and 53 Change in levels of serum ferritin from baseline to 3, 6, 9 and 12 months (Weeks 13, 25, 37 and 53).
Treatment Compliance to Deferasirox up to 1 year Treatment compliance was assessed using records of study medication used, dosages administered, and intervals between visits during the study. Drug accountability was noted by the field monitor during site visits and at the completion of the trial. Participants were asked to return all unused medication at monthly visits.
The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations up to Week 13 (Month 3) HFE (hemochromatosis) gene mutations in the Myelodysplastic Syndrome (MDS) population, the trial included testing for the C282Y, H63D and S65C HFE gene mutations. One blood sample was collected at Baseline (Week 1), or, if that visit was missing, the sample was taken at Week 13 (Month 3). Only one blood sample was to be taken from each participant.
Total Iron Levels From Baseline to Weeks 13, 25, 37, 49 and 53 Levels of non-transferrin bound iron (NTBI) and serum iron from baseline to 3,6,9 and 12 months (Weeks 13, 25, 37 and 49) were assessed.
Directly Chelatable Iron (DCI) From Baseline to Weeks 13, 25, 37 and 49 The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.
Transfusion Requirements up to 1 year Number of participants receiving transfusions, the summarized during the study.
Serum Transferrin Levels From Baseline to Weeks 13, 25, 37, 49 and 53 Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.
Transferrin Saturation From Baseline to Weeks 13, 25, 37, 49 and 53 Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.
Frequency of Hematologic Improvement During the Study up to 1 year Hematologic responses defined by International Working Group response criteria in myelodysplasia. Hematologic Improvement (HI) responses, at least 9 weeks defined as:
Erythroid response (pretreatment, \<11 g/dL): Hgb increase by 1.5 g/dL; Relevant reduction units of Red blood cell (RBC) transfusions by absolute number at least 4 RBC transfusions/8 week compared with pretreatment transfusion number in previous 8 weeks; Only RBC transfusions for Hgb of 9.0 g/dL pretreatment count in RBC transfusion response evaluation; Platelet response (pretreatment,\<100x10\^9/L): If starting with \>20x10\^9/L platelets: absolute increase 30x10\^9/L, Increase from baseline \<20 x10\^9/L to \>20x10\^9/L and by =/\> 100%; Neutrophil response (pretreatment, \<1.0x10\^9/L): =/\> 100% increase \& absolute increase \>0.5x10\^9/L; Progression or relapse after HI: At least 1 of the following: =/\>50% decrement from max response levels in granulocytes or platelets; Reduction in Hgb by 1.5 g/dL; or Transfusion dependence.Trough Plasma Deferasirox Concentration At Week 13, 25, 37 and 49 The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.
Trial Locations
- Locations (36)
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Cedars-Sinai Medical Center, UCLA School of Medicine
🇺🇸Los Angeles, California, United States
Bay Area Cancer Research Group
🇺🇸Concord, California, United States
Novartis Investigative Site
🇨🇦Montreal, Quebec, Canada
Straub Clinic and Hospital
🇺🇸Honolulu, Hawaii, United States
Emory University School of Medicine/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
St. Agnes HealthCare
🇺🇸Baltimore, Maryland, United States
Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital
🇺🇸Alexandria, Louisiana, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
University of Chicago Hospital
🇺🇸Chicago, Illinois, United States
Rochester General Hospital/Lipson Cancer and Blood Center
🇺🇸Rochester, New York, United States
Western Pennsylvania Hospital Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
NMOHC
🇺🇸Albuquerque, New Mexico, United States
Arlington Fairfax Hematology Oncology PC
🇺🇸Arlington, Virginia, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
The West Cancer Clinic
🇺🇸Memphis, Tennessee, United States
Rush Cancer Institute Univ. of Massachussets Medical Center
🇺🇸Worcester, Massachusetts, United States
University of Kentucky College of Medicine, Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
The Center for Cancer Care & Research (TCCCR)
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Center
🇺🇸Buffalo, New York, United States
Cancer Care of WNC
🇺🇸Asheville, North Carolina, United States
Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Baylor/The Methodist Hospital
🇺🇸Houston, Texas, United States
The Cancer Center at Hackensack University
🇺🇸Hackensack, New Jersey, United States
Wake Forest UniversitComprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Novartis Investigative site
🇺🇸Nashville, Tennessee, United States
Univ of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
UCSF
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
Oncology Hematology West, PC
🇺🇸Omaha, Nebraska, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States