Clinical trial NCT00631163: Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional Hemosiderosis
Official title: A Multi-Center, Open-label, Non Comparative, Phase II Trial on Efficacy and Safety of ICL670 Given for 1 Year With Dose Adjustments Based on Serum Ferritin in Patients With Chronic Anemia and Transfusional Hemosiderosis Including an Additional 1 Year Extension.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Anemia
Transfusional Hemosiderosis
Keywords: Iron Overload,
Chelation,
MDS,
Chronic Anemia,
Deferasirox,
Transfusional hemosiderosis,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-03-07
Enrollment: 102
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 overall purpose of this trial is to further evaluate the efficacy and safety of deferasirox, dosed initially according to the transfusional iron intake, in patients with transfusion dependant anemia related to disorders other than β-thalassemia and sickle cell disease.

During the study, the dose will be adjusted based on serum Ferritin.The overall purpose of the extension is to allow further treatment of patients who have already completed the core study, and to enable collection of long term efficacy and safety data. Patients will continue to receive Deferasirox at the dose they received at the end of the core study.


Eligibility criteria: Inclusion criteria (Core):

* Patients with transfusional iron overload due to:
* low or intermediate (INT-1) risk Myelodysplastic Syndrome (MDS)determined via International Prognosis Scoring System (IPSS) criteria
* other congenital or acquired anemias excluding B-thalassemia and sickle cell disease
* Lifetime transfusion history of ≥20 unit (approximately 100 mL/kg) of packed red blood cells or showing evidence of iron overload (serum ferritin \>1000 µg/L).
* Able to provide written informed consent
* Life expectancy ≥ 12 months If patient was previously treated with deferiprone, a washout period of one month should occur before the first dose of deferasirox

Inclusion criteria (Extension):

* Patients completing the planned 12-month core study (CICL670A2204).
* Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with national legislation.

Exclusion criteria (Core and Extension):

* Patients with β-thalassemia, sickle cell disease or myelodysplastic syndrome with an IPSS score being Intermediate-2 or High.
* Patients with serum creatinine \> ULN
* Patients with ALT(SGPT) levels \> 5 x ULN
* Significant proteinuria as indicated by a urinary protein/creatinine ratio \>0.5 mg/mg in a non-first void urine sample on two assessments during the screening period.
* History of HIV positive test result , or of clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range)
* Patients on investigational MDS therapies, including lenalidomide, thalidomide, azacitidine and arsenic trioxide, must have a ≥ 4 week washout period prior to the first dose of study drug.
* Patients with systemic uncontrolled hypertension
* Patients with unstable cardiac disease not controlled by standard medical therapy
* Systemic disease (cardiovascular, renal, hepatic, etc.) which would prevent study treatment
* Pregnancy (as documented in required screening laboratory test) or breast feeding.
* Patients treated 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
* Patients being considered by the investigator potentially unreliable and/or not cooperative with regard to the study protocol
* History of hypersensitivity to any of the study drug or excipients
* Sexually active pre-menopausal female patients without adequate contraception. Female patients must use effective contraception or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.

Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1
timeFrame: From the Baseline, Year 1 (End of core study)
Secondary outcomes:
measure: Absolute Change From Baseline in Liver Iron Concentration (LIC) to End of Year 2
timeFrame: From the Baseline to End of Year 2 (End of extension study)
measure: Absolute Change From Baseline in Liver Iron Concentration (LIC) in Japanese Subgroup
timeFrame: From the Baseline, End of Year 1 (End of core study), End of Year 2 (End of extension study)
measure: Absolute Change From Baseline in Serum Ferritin Levels to Year 2
timeFrame: From the Baseline up to Year 2 (End of extension study)
measure: Absolute Serum Ferritin Levels Over 2 Years
timeFrame: From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)
measure: Total Body Iron Elimination Rate (TBIE), Iron Intake, Iron Excretion/Iron Intake and Chelation Efficiency After 2 Years
timeFrame: From the Baseline, Year 2 (End of extension study)
measure: Correlation of LIC and Serum Ferritin at Core and Extension Study
timeFrame: From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESI), Discontinuation and Interruption
timeFrame: From the Baseline up to Year 2 (End of extension study)
measure: Number of Participants With Clinically Significant Ophthalmological Abnormalities
timeFrame: At 2 years (End of extension study)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Nishinomiya
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kahoku-gun
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: OsakaSayama
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Shimotsuka-gun
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Simotsuke-city
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Cyuo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Kumamoto
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Nagasaki
country: Japan
facility: Novartis Investigative Site
city: Toyama
country: Japan
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Adana
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Pharmeceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Kohgo Y, Urabe A, Kilinc Y, Agaoglu L, Warzocha K, Miyamura K, Lim LC, Glaser S, Wang C, Wiktor-Jedrzejczak W. Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias. Acta Haematol. 2015;134(4):233-42. doi: 10.1159/000381893.