allogeneic hematopoietic cell transplantation with iron overload MedDRA version: 9.1 Level: LLT Classification code 10001756 Term: Allogenic bone marrow transplantation therapy
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Transfusional iron overload three to six months after HCT (mean serum ferritin level > 1000 ng/ml) with no evidence of active inflammation (C-reactive protein [CAP] 1000 /mm³. 3. History of at least 20 units of red blood cell transfusions or 100mL/kg of prepacked red blood cells (PRBCs). 4. Patients of either gender and age = 18 years. 5. Female patients who have reached menarche and who are sexually active must use double-barrier contraception, oral contraceptive plus barrier contraception , or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months. Only contraception with a pearl-Index below 1% should be considered. 6. Written informed consent by the patient. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Non-transfusion related hemosiderosis 2. Active malignancy 3. Known active viral hepatitis or known HIV positiveness 4. Mean levels of alanine aminotransferase (ALT) > 5x ULN 5. Treatment with any iron chelator after HCT 6. Uncontrolled systemic hypertension 7. Serum creatinine > 1.5 ULN 8. History of nephrotic syndrome. 9. Previous history of clinically relevant ocular toxicity related to iron chelation. 10. Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment 11. Psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment. 12. Pregnant or breast feeding patients. 13. Treatment with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days as well as the simultaneous participation in other clinical trials. 14. Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following: • history of inflammatory bowel syndrome, ulcers, gastrointestinal or rectal bleeding; • history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; • history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase; • history of urinary obstruction or difficulty in voiding 15. History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative. 16. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening period. 17. QT > 470 msec on screening ECG. 18. Torsades de Pointes risk (patients with congenital long QT syndrome, heart insufficiency NYHA II-IV etc.). 19. Active GVHD at the time of enrolment. 20. History of clinically relevant auditory toxicity in combination with chelation therapy. 21. Galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption. 22. Simultaneous consumption of aluminium-containing antacid preparations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate if ICL670 can provide clinically acceptable chelation, as measured by serum ferritin to patients presenting with iron overload three to six months after related or unrelated HCT (serum ferritin levels of = 1000 ng/ml) irrespective of conditioning regimen.;Primary end point(s): The primary efficacy variable is the change from baseline in serum ferritin at week 52.;Secondary Objective: • To evaluate the relationship between serum ferritin and transferrin (TRF) and transferrin saturation. • To evaluate factors related to iron stores in the participating patients (number of blood transfusions from diagnosis, HFE genotype of patients after HCT, Hepcidin after HCT) which may (1) influence iron body stores after HCT and (2) play a key role in determining response to treatment with ICL670. • To evaluate the possible influence of ICL670 on the absorption of Cyclosporine A and to monitor immunosuppression by measuring trough Cyclosporine A levels. • To assess the incidence of chronic graft-versus-host disease ("limited" or "extensive") at day 365 post-transplant according to Shulman criteria. • To evaluate the safety and tolerability profile of ICL670 in patients after HCT with evidence of iron overload treated for up to 52 weeks. • To explore the potential of SQUID as a method for non-invasive assessment of organ specific iron overload in a subset of patients. | — |
Countries
Germany
Outcome results
None listed