Clinical trial NCT00110266: Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients
Official title: An Open Label, Safety and Tolerability Study of Deferasirox for Treatment of Transfusional Iron Overload in Low-risk and INT-1, Myelodysplastic Patients Using Serum Ferritin Monitoring
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Iron Overload
Keywords: ICL670
Deferasirox
Iron chelation
Chelator
Desferal
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-05-05
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants Reporting Adverse Events
timeFrame: up to 53 Weeks
Secondary outcomes:
measure: Change in Serum Ferritin From Baseline to Weeks 13, 25, 37 and 53
timeFrame: From Baseline to Weeks 13, 25, 37 and 53
measure: Change in Labile Plasma Iron (LPI)
timeFrame: From Baseline to Weeks 13, 25, 37 and 49
measure: Directly Chelatable Iron (DCI)
timeFrame: From Baseline to Weeks 13, 25, 37 and 49
measure: Total Iron Levels
timeFrame: From Baseline to Weeks 13, 25, 37, 49 and 53
measure: Serum Transferrin Levels
timeFrame: From Baseline to Weeks 13, 25, 37, 49 and 53
measure: Transferrin Saturation
timeFrame: From Baseline to Weeks 13, 25, 37, 49 and 53
measure: Transfusion Requirements
timeFrame: up to 1 year
measure: Frequency of Hematologic Improvement During the Study
timeFrame: up to 1 year
measure: Trough Plasma Deferasirox Concentration
timeFrame: At Week 13, 25, 37 and 49
measure: Treatment Compliance to Deferasirox
timeFrame: up to 1 year
measure: The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations
timeFrame: up to Week 13 (Month 3)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ of Alabama Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Concord
country: United States
facility: Bay Area Cancer Research Group
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, UCLA School of Medicine
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute
state: Georgia
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky College of Medicine, Markey Cancer Center
state: Kentucky
city: Alexandria
country: United States
facility: Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital
state: Louisiana
city: Baltimore
country: United States
facility: St. Agnes HealthCare
state: Maryland
city: Worcester
country: United States
facility: Rush Cancer Institute Univ. of Massachussets Medical Center
state: Massachusetts
city: Southfield
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: The Center for Cancer Care & Research (TCCCR)
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West, PC
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University
state: New Jersey
city: Albuquerque
country: United States
facility: NMOHC
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital/Lipson Cancer and Blood Center
state: New York
city: Asheville
country: United States
facility: Cancer Care of WNC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest UniversitComprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital Cancer Institute
state: Pennsylvania
city: Memphis
country: United States
facility: The West Cancer Clinic
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative site
state: Tennessee
city: Houston
country: United States
facility: Baylor/The Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Arlington
country: United States
facility: Arlington Fairfax Hematology Oncology PC
state: Virginia
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: List AF, Baer MR, Steensma DP, Raza A, Esposito J, Martinez-Lopez N, Paley C, Feigert J, Besa E. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012 Jun 10;30(17):2134-9. doi: 10.1200/JCO.2010.34.1222. Epub 2012 Apr 30.