Study of Deferasirox for Treatment of Transfusional Iron Overload in Myelodysplastic Patients

Myelodysplastic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00110266
• Other study ID #: CICL670AUS03
• Status: Completed
• Phase: Phase 2
• Start date: July 25, 2005
• Est. completion date: March 28, 2008

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00343837

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: March 28, 2008
• Est. primary completion date: March 28, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Iron Overload
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes

Intervention

Drug:
• Deferasirox
20 mg/kg/day over one year in patients with MDS

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
United States	NMOHC	Albuquerque	New Mexico
United States	Cabrini Center for Cancer Care/Christus St. Frances Cabrini Hospital	Alexandria	Louisiana
United States	Arlington Fairfax Hematology Oncology PC	Arlington	Virginia
United States	Cancer Care of WNC	Asheville	North Carolina
United States	Emory University School of Medicine/Winship Cancer Institute	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	St. Agnes HealthCare	Baltimore	Maryland
United States	Univ of Alabama Birmingham	Birmingham	Alabama
United States	Roswell Park Cancer Center	Buffalo	New York
United States	Novartis Investigative Site	Chicago	Illinois
United States	University of Chicago Hospital	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Bay Area Cancer Research Group	Concord	California
United States	City of Hope National Medical Center	Duarte	California
United States	The Cancer Center at Hackensack University	Hackensack	New Jersey
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Baylor/The Methodist Hospital	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky College of Medicine, Markey Cancer Center	Lexington	Kentucky
United States	Cedars-Sinai Medical Center, UCLA School of Medicine	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	The West Cancer Clinic	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Novartis Investigative site	Nashville	Tennessee
United States	Oncology Hematology West, PC	Omaha	Nebraska
United States	Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Phoenix	Arizona
United States	Western Pennsylvania Hospital Cancer Institute	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Rochester General Hospital/Lipson Cancer and Blood Center	Rochester	New York
United States	The Center for Cancer Care & Research (TCCCR)	Saint Louis	Missouri
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	UCSF	San Francisco	California
United States	UCSF	San Francisco	California
United States	Novartis Investigative Site	Southfield	Michigan
United States	Novartis Investigative Site	Spokane	Washington
United States	Wake Forest UniversitComprehensive Cancer Center	Winston-Salem	North Carolina
United States	Rush Cancer Institute Univ. of Massachussets Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Reporting Adverse Events	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.	up to 53 Weeks
Secondary	Change in Serum Ferritin 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).	From Baseline to Weeks 13, 25, 37 and 53
Secondary	Change in Labile Plasma Iron (LPI)	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	From Baseline to Weeks 13, 25, 37 and 49
Secondary	Directly Chelatable Iron (DCI)	The blood sample for DCI determinations were collected at Week 1 (prior to first dose) and at Weeks 13, 25, 37 and 49.	From Baseline to Weeks 13, 25, 37 and 49
Secondary	Total Iron Levels	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.	From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary	Serum Transferrin Levels	Serum transferrin from baseline to 3, 6, 9 and 12 months of treatment (Visit Weeks 13, 25, 37 and 49) were assessed.	From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary	Transferrin Saturation	Levels of transferrin saturation from baseline to 3, 6, 9 and 12 months.	From Baseline to Weeks 13, 25, 37, 49 and 53
Secondary	Transfusion Requirements	Number of participants receiving transfusions, the summarized during the study.	up to 1 year
Secondary	Frequency of Hematologic Improvement During the Study	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.	up to 1 year
Secondary	Trough Plasma Deferasirox Concentration	The Pharmacokinetic (PK) parameters were assessed at Week 13, 25, 37 and 49 using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method.	At Week 13, 25, 37 and 49
Secondary	Treatment Compliance to Deferasirox	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.	up to 1 year
Secondary	The Prevalence of Hereditary Hemochromatosis Gene (HFE) Gene Mutations	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.	up to Week 13 (Month 3)

External Links

•   Publication (Embasse # 2012421150)
•   Publication (Embasse # 2012421150)
•   Results for CICL670AUS03 from the Novartis Clinical Trials website