Clinical trial NCT01044186: A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity
Official title: A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transfusional Iron Overload
Keywords: Deferasirox
ICL670A
Iron chelators
Deferiprone
Transfusional hemosiderosis
Congenital aplastic anemia (Diamond Blackfan anemia)
Red cell aplasia
Thalassemia
β thalassemia
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-01-07
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, non-comparative, multi-center protocol was to further evaluate safety and to provide treatment with ICL670 to patients who had or were at risk of life threatening complications due to transfusional iron overload with a documented inability to tolerate any of the commercially available iron chelators due to severe toxicity rendering continued therapy either impossible or hazardous. Patients who were also ineligible for all on-going registration trials with ICL670 were included in the study. In exceptional cases, patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for the registration trials were also enrolled provided they had a well-documented, sound justification for alternative chelation therapy.


Eligibility criteria: Inclusion Criteria:

* Patients had to be at risk of life-threatening complications due to transfusional iron overload and be unable to tolerate therapy with any of the commercially available iron chelators (mainly deferoxamine and/or deferiprone) because of documented severe toxicity.
* Patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for other trials with ICL670 could also be enrolled providing they had a well-documented, sound justification for alternative chelation therapy.
* Serum ferritin ≥ 8000 μg/L.
* Serum ferritin \< 8000μg/L and LIC of ≥ 7 mg Fe/g dry weight.
* Patients for whom ≥ 8 blood transfusions per year were required in order to maintain the Hemoglobin level at \> 9 g/dL.
* Female patients who have reached menarche and who were sexually active had to use double barrier contraception (oral plus barrier contraception), or had to have undergone total hysterectomy and/or ovariectomy, or tubal ligation.
* Written, voluntary informed consent.

Exclusion Criteria:

* Patients with transfusional iron overload who were not experiencing severe toxicities during therapy with other iron chelators (e.g. deferoxamine and/or deferiprone).
* Patients with non-transfusional hemosiderosis.
* Patients with severe liver failure as defined by a score of ≥ 10 points on the Child-Pugh scale.
* Patients with serum creatinine 1.5 times the upper limit of normal (ULN) at screening.
* Patients with a history of nephrotic syndrome.
* Patients with a diagnosis of clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation therapy.
* Patients with severe systemic diseases unrelated to iron overload and which would prevent them from undergoing treatment with ICL670.
* Patients with psychiatric or addictive disorders which prevent them from giving informed consent or undergoing treatment with ICL670.
* Pregnant or breast feeding patients.
* Patients treated with systemic investigational drugs within the past four weeks or topical investigational drugs within the past seven days.
* Any surgical or medical condition which might significantly alter the absorption or excretion of drugs as shown by evidence of any of the following:

  * History of inflammatory bowel disease
  * History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
  * History of pancreatic injury or pancreatitis; indication of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
* Patients being considered by the investigator as potentially unreliable and/or not cooperative with regard to the protocol.
* History of drug or alcohol abuse within the 12 months prior to dosing.

Primary outcomes:
measure: To evaluate the safety profile and to provide treatment with ICL670 for patients with or at risk of life-threatening complications due to transfusional iron overload who are unable to tolerate other iron chelators because of documented severe toxicity.
timeFrame: 0 - 163 weeks
Secondary outcomes:
measure: To estimate the absolute and relative change of liver iron concentration (LIC), to be measured using appropriate methodology available at individual centers.
timeFrame: Yearly
measure: To evaluate the role of serum ferritin, serum iron, transferrin and transferrin saturation in monitoring iron burden in these patients.
timeFrame: Quarterly
measure: To evaluate the relationship between changes in LIC and serum ferritin, transferring saturation and serum iron.
timeFrame: Yearly
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital and Research Center - Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Jamaica
country: United States
facility: Queens Hospital Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: New York Methodist Hospital
state: New York
city: Cincinnatti
country: United States
facility: Cincinnatti Children's Hospital Medical center
state: Ohio
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Athens
country: Greece
facility: Novartis investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
city: Brindisi
country: Italy
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
city: Cosenza
country: Italy
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Modena
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Torino
country: Italy
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: