transfusion-dependent thalassemia or myelodysplastic syndrome at very low, low or intermediate (int-1) risk MedDRA version: 16.1 Level: LLT Classification code 10054658 Term: Thalassemia System Organ Class: 100000004850 MedDRA version: 16.1 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864
Conditions
Interventions
Product Code: ICL670
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Current Sponsor code: DEFERASIROX
Other descriptive name: DEFERASIROX
Concentratio
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent/assent before any study-specific procedures. For pediatric patients, consent will be obtained from parent(s) or legal patient?s representative. Investigators will also obtain assent of patients according to local, regional or national guidelines. 2. Male and female patients aged ? 10 years 3. Patients with transfusion-dependent thalassemia and iron overload, requiring deferasirox DT at doses of ? 30 mg/kg/day as per the investigator?s decision OR Patients with very low, low or intermediate (int-1) risk myelodysplastic syndrome (MDS) and iron overload, requiring deferasirox DT at doses of ? 20 mg/kg/day as per the investigator?s decision. ? The very low, low or intermediate (int-1) risk MDS should be determined by the Revised International Prognostic Scoring System (IPSS-R) and IPSS-R must be confirmed by a bone marrow examination within 6 months prior to study entry and must be hematologically stable with a patient?s life expectancy of at least 1 year. 4. History of transfusion of at least 20 PRBC units and anticipated to be transfused with at least 8 units of PRBCs annually during the study 5. Serum ferritin > 1000 ng/mL, measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria) Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 105 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Creatinine clearance below the contraindication limit in the locally approved prescribing information. Creatinine clearance will be estimated from serum creatinine at screening Visit 1 and screening Visit 2 and the mean value will be used for eligibility criteria. 2. Serum creatinine > 1.5 xULN at screening measured at screening Visit 1 and screening Visit 2 (the mean value will be used for eligibility criteria). 3. ALT (SGPT) > 5xULN, unless if LIC confirmed as 0.5 mg/mg in a non-first void urine sample at screening Visit 1 or screening Visit 2. 5. Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 6. 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). 7. Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol (including use of electronic devices for ePRO). 8. Patients with a known history of HIV seropositivity (Elisa or Western blot). 9. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin. 10. Patients participating in another clinical trial or receiving an investigational drug. 11. History of hypersensitivity to any of the study drug or excipients. 12. Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.). 13. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. 14. Sexually active males unless they use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall safety of deferasirox FCT and deferasirox DT formulations in patients with transfusion-dependent thalassemia or myelodysplastic syndrome at low or intermediate (int-1) risk.;Secondary Objective: - To evaluate both formulations on selected GI AEs - To evaluate pharmacokinetics of both formulations - To evaluate both formulations on patient satisfaction and palatability using a Patient Reported Outcomes (PRO) questionnaire - To evaluate both formulations on patient?s GI symptoms using a PRO daily diary - To evaluate both formulations on patient compliance using pill count and a PRO daily diary;Primary end point(s): Overall safety, as measured by frequency and severity of adverse events and changes in laboratory values from baseline (serum creatinine, creatinine clearance, ALT, AST, platelets, RBC and WBC);Timepoint(s) of evaluation of this end point: weekly for first 4 weeks and then every 4 weeks until end of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Frequency of selected GI AEs (diarrhea, constipation, nausea, vomiting, abdominal pain) 2) PK parameters 3) Domain scores of treatment satisfaction and palatability over time 4) Weekly average of daily scores of GI diary 5) Relative consumed FCT/DT counts 6) Patient-reported medication consumption;Timepoint(s) of evaluation of this end point: 1) weekly for first 4 weeks and then every 4 weeks until end of treatment 2) ? AUCtau, AUClast, Cmax, Tmax at week 1 and week 3 (only applies to PK subset A) ? C2hr and Ctrough at week 3, 13 and 21 for all study patients 3) week 2, 3 and 13and last day of treatment 4) daily completion of questionnaire until last day of treatment 5) monthly 6) daily completion of questionnaire until last day of treatment | — |
Countries
Austria, Belgium, Canada, France, Germany, Greece, Italy, Japan, Spain, Thailand, Tunisia, United Kingdom, United States
Contacts
Public ContactDepartamento Médico Oncología (GMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed