Comparing Therapies for the Treatment of Severe Aplastic Anemia
Kľúčové slová
Abstrakt
Popis
Severe aplastic anemia (SAA) is a disorder with a poor prognosis if untreated. Current accepted therapeutic strategies include bone marrow transplantation (BMT) and immunosuppression, both offering cure or amelioration in the majority of patients. Although BMT is successful using human leukocyte antigen (HLA) matched sibling bone marrow, the 25% probability of finding an HLA identical sibling within a family renders this approach available to only a minority of patients. BMT utilizing HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common, occurring in about a third of responders. Late evolution of aplastic anemia to other serious hematologic disorders is a significant problem following successful treatment with ATG/CSA with paroxysmal nocturnal hemoglobinuria (PNH) occurs in approximately 13%, myelodysplasia in about 10%, and acute leukemia in about 7%. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in 10 patients. In this small group, the overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not seen during a median follow-up of greater than 10 years. In the larger randomized trial proposed here, we will compare sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high dose cyclophosphamide and CSA. Secondary endpoints include response duration, event free survival, and overall survival.
Termíny
| Naposledy overené: | 08/31/2020 |
| Prvý príspevok: | 11/02/1999 |
| Odhadovaná registrácia bola odoslaná: | 11/02/1999 |
| Prvý príspevok: | 11/03/1999 |
| Posledná aktualizácia bola odoslaná: | 09/20/2020 |
| Posledná aktualizácia bola zverejnená: | 09/21/2020 |
| Aktuálny dátum začatia štúdie: | 06/01/1997 |
| Odhadovaný dátum dokončenia primárneho okruhu: | 02/19/2001 |
| Odhadovaný dátum dokončenia štúdie: | 03/02/2008 |
Stav alebo choroba
Intervencia / liečba
Drug: B
Drug: A
Drug: cyclosporine
Fáza
Skupiny zbraní
| Arm | Intervencia / liečba |
|---|---|
| Experimental: A D1-4 cyclophosphamide 50 mg/kg IV, then cyclosporine starting on d14 at 12 mg/kg/d for 6 months | Drug: A cyclophosphamide |
| Experimental: B ATG at 40 mg/kg/d for 4 days then cyclosporine at 12 mg /kg/d for 6 months | Drug: B antithymocyte globulin |
Kritériá oprávnenosti
| Vek vhodný na štúdium | 15 Years To 15 Years |
| Pohlavia vhodné na štúdium | All |
| Prijíma zdravých dobrovoľníkov | Áno |
| Kritériá | - INCLUSION CRITERIA: Severe aplastic anemia confirmed at NIH by: 1. Bone marrow cellularity less than thirty percent (excluding lymphocytes). 2. At least two of the following: Absolute neutrophil count less that 500/mm(3); Platelet count less than 20,000/mm(3); Reticulocyte count less than 60,000/mm(3). EXCLUSION CRITERIA: Serum creatinine greater than to 2.5 mg/dl. Cardiac ejection fraction less than 45% by MUGA. Underlying carcinoma (except local cervical, basal cell, squamous cell or melanoma). Current pregnancy or unwilling to take oral contraceptives. Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes. Evidence of a clonal disorder on cytogenetics. HIV positivity. Inability to understand the investigational nature of the study. Patients who are moribund or have hepatic, renal, cardiac, metabolic or other concurrent diseases of such severity that death within 7-10 days is likely. Previous treatment with ATG, or cyclophosphamide. |
Výsledok
Primárne výstupné opatrenia
1. Compare the sustained response proportions among patients with SAA treated with immunosuppressive therapy with either ATG/CSA or high dose cyclophosphamide and CSA. [12 weeks.]
Opatrenia sekundárnych výsledkov
1. Overall and event-free survival. [12 months]
2. Response duration. Evolution to PNH, myelodysplasia, and active leukemia. [12 months]
