Eculizumab in Treating Patients With Paroxysmal Nocturnal Hemoglobinuria
Açar sözlər
Mücərrəd
Təsvir
OBJECTIVES:
Primary
- Determine the safety of eculizumab in patients with transfusion-dependent hemolytic paroxysmal nocturnal hemoglobinuria.
- Determine the efficacy of this drug, in terms of hemoglobin stabilization and the number of packed red blood cell units transfused during the 26-week treatment period, in these patients.
Secondary
- Compare the occurrence of transfusion avoidance, hemolysis (measured by lactate dehydrogenase [LDH] area under the curve), and the changes in fatigue during the 26-week treatment period in patients treated with this drug vs placebo.
- Compare LDH changes, quality of life changes, thrombosis, platelet activity, nitric oxide, and free hemoglobin measures during the 26-week treatment period in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to the number of packed red blood cell (PRBC) units transfused 1 year prior to screening (< 15 units vs 15-25 units vs > 25 units). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Within 10 days after PRBC transfusion (administered during the study observation period), patients receive placebo IV over 30 minutes once a week for 5 weeks and then once every 2 weeks for 21 weeks.
- Arm II: Within 10 days after PRBC transfusion (administered during the study observation period), patients receive eculizumab IV over 30 minutes once a week for 5 weeks and then once every 2 weeks for 21 weeks.
Quality of life is assessed at baseline; at weeks 0-4, 12, 20, and 26 during study treatment; then at weeks 1, 2, 4, and 8 after completion of study treatment.
After completion of study treatment, patients are followed at weeks 1, 2, 4, and 8.
PROJECTED ACCRUAL: Approximately 75 patients (37 per treatment arm) will be accrued for this study.
Tarixlər
| Son Doğrulandı: | 05/31/2005 |
| İlk təqdim: | 06/01/2005 |
| Təxmini qeydiyyat təqdim edildi: | 06/01/2005 |
| İlk Göndərmə: | 06/02/2005 |
| Son Yeniləmə Göndərildi: | 05/28/2013 |
| Son Yeniləmə Göndərildi: | 05/29/2013 |
| Həqiqi Təhsilin Başlama Tarixi: | 10/31/2004 |
| Təxmini İşin Tamamlanma Tarixi: | 05/31/2005 |
Vəziyyət və ya xəstəlik
Müdaxilə / müalicə
Biological: eculizumab
Faza
Uyğunluq Kriteriyaları
| Təhsil üçün uyğun yaşlar | 18 Years Üçün 18 Years |
| Təhsilə Uyğun Cinslər | All |
| Sağlam Könüllüləri qəbul edir | Bəli |
| Kriteriyalar | DISEASE CHARACTERISTICS: - Diagnosis of paroxysmal nocturnal hemoglobinuria - Must have required ≥ 4 episodes of transfusions for anemia or anemia-related symptoms within the past year - Mean pre-transfusion hemoglobin ≤ 10. 5 g/dL over the past year - Glycosylphosphatidylinositol (GPI)-deficient red blood cell clone (type III cells) of ≥ 10% by flow cytometry - Must have received 1 packed red blood cell transfusion during the study observation period (within 48 hours of the hemoglobin level that precipitated the transfusion) and within 1.5 g/dL of the mean pre-transfusion hemoglobin level over the past year - Pre-transfusion hemoglobin ≤ 9 g/dL with symptoms - Pre-transfusion hemoglobin ≤ 7 g/dL without symptoms - Received Neisseria meningitidis vaccination at least 2 weeks before initiation of study therapy PATIENT CHARACTERISTICS: Age - 18 and over Performance status - Not specified Life expectancy - Not specified Hematopoietic - See Disease Characteristics - Absolute neutrophil count > 500/mm^3 - Platelet count ≥ 100,000/mm^3 Hepatic - Lactate dehydrogenase ≥ 1.5 times upper limit of normal Renal - Not specified Immunologic - No known or suspected active bacterial infection - No recurrent bacterial infections - No history of meningococcal disease Other - No known or suspected hereditary complement deficiency - No other condition that would increase the patient's risk or confound the outcome of the study - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy - See Disease Characteristics - No prior bone marrow transplantation - Concurrent epoetin alfa allowed* Chemotherapy - Not specified Endocrine therapy - Concurrent corticosteroids allowed** Radiotherapy - Not specified Surgery - Not specified Other - More than 30 days since prior participation in another investigational drug trial - More than 30 days since prior investigational agents, devices, or procedures - Concurrent immunosuppressants allowed* - Concurrent warfarin allowed provided INR level is stable for the past 4 weeks and expected to remain stable during observation and study treatment - Concurrent iron supplements or folic acid allowed** - Concurrent low-molecular weight heparin allowed** NOTE: *Provided dose is stable for the past 26 weeks and during study observation and treatment NOTE: **Provided dose is stable for the past 4 weeks and expected to remain stable (or decrease for corticosteroids) during study observation and treatment |
