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

Condition(s) targeted: Myelodysplastic Syndrome; Iron Overload

Intervention: Deferasirox (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis, Study Chair, Affiliation: Novartis

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.

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 design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: 12 month safety in patients with myelodysplastic syndrome (MDS)

Secondary outcome:

Changes in serum ferritin from baseline to 3, 6, 9 and 12 months after initiating treatment

Effect of non-transferrin bound iron (NTBI), serum iron, transferrin and transferrin saturation on the safe administration of deferasirox

Changes in transfusion requirements, serum erythropoietin levels, and estimated frequency of hematologic improvement in patients who are not receiving growth factors or chemotherapy for their underlying MDS.

Trough pharmacokinetic parameters of deferasirox in patients with MDS

Drug accountability

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

- 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)

- 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

Univ of Alabama Birmingham, Birmingham, Alabama 35294, United States

Mayo Clinic, Scottsdale, Arizona 85259, United States

Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California 90048, United States

UCSF, San Francisco, California 94143-0324, United States

City of Hope National Medical Center, Duarte, California 91010, United States

Bay Area Cancer Research Group, Concord, California 94520, United States

UCSF, San Francisco, California 94143, United States

UCLA Medical Center, Los Angeles, California 90095-1678, United States

Rocky Mountain Cancer Centers, Aurora, Colorado 80012, United States

Mayo Clinic, Jacksonville, Florida 32224, United States

Winship Cancer Institute, Atlanta, Georgia 30322, United States

Straub Clinic and Hospital, Honolulu, Hawaii 96813, United States

University of Chicago Hospital, Chicago, Illinois 60637-1470, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

University of Kentucky College of Medicine, Markey Cancer Center, Lexington, Kentucky 40536-0093, United States

Cabrini Center for Cancer Care, Alexandria, Louisiana 71301, United States

St. Agnes HealthCare, Baltimore, Maryland 21231-1000, United States

Rush Cancer Institute Univ. of Massachussets Medical Center, Worchester, Massachusetts 01605, United States

Mayo Clinic, Rochester, Minnesota 55905, United States

The Center for Cancer Care & Research (TCCCR), St. Louis, Missouri 63110, United States

Oncology Hematology West, PC, Omaha, Nebraska 68124-2346, United States

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756-0001, United States

Local Institution, Hackensack, New Jersey 07601, United States

NMOHC, Albuquerque, New Mexico 87109, United States

Roswell Park Cancer Center, Buffalo, New York 14623, United States

Rochester General Hospital, Rochester, New York 14621, United States

Wake Forest University, Winston Salem, North Carolina 27157-1082, United States

Cancer Care of WNC, Asheville, North Carolina 28801, United States

The Ohio State University, Columbus, Ohio 43210, United States

The Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States

Thomas Jefferson University; Jefferson Medical College, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, United States

Western Pennsylvania Hospital; Cancer Institute, Pittsburgh, Pennsylvania 15224, United States

The West Cancer Clinic, Memphis, Tennessee 38120, United States

Baylor/Methodist, Houston, Texas 77030, United States

Utah Cancer Specialists, Salt Lake City, Utah 84106, United States

Arlington Fairfax Hematology Oncology PC, Arlington, Virginia 22205, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Starting date: May 2005
Ending date: December 2006
Last updated: June 5, 2008