Comparing Therapies for the Treatment of Severe Aplastic Anemia
Condition: Severe Aplastic Anemia (SAA)
MeSH terms: Anemia; Anemia, Aplastic
Study type: Interventional
Phase: Phase 2

Summary: 
      Severe Aplastic Anemia (SAA) is a rare and very serious blood disorder in which the bone
      marrow stops producing the cells which make up blood; red blood cells, white blood cells, and
      platelets.

      Researchers believe this is caused by an autoimmune reaction, a condition in which the
      natural defense system of the body begins attacking itself. In SAA the immune system begins
      attacking the bone marrow. Red blood cells are responsible for carrying oxygen to all of the
      organ systems in the body, and low numbers (anemia) can cause difficulty breathing and
      fatigue. Platelets are responsible for normal blood clotting and low numbers can result in
      easy bruising and bleeding which can be deadly. White blood cells are responsible for
      fighting infections, and low numbers of these can lead to frequent infections, the most
      common cause of death in patients with aplastic anemia.

      SAA can be treated by bone marrow transplant (BMT) or by drugs designed to slow down the
      immune system (immunosuppressants). BMT can be successful, but it requires a donor with
      matched bone marrow, making this therapy available only to a few patients. BMT with unmatched
      bone marrow can fail and cause dangerous side effects.

      Presently, the two drugs used to treat SAA by slowing down the immune system
      (immunosuppression) are antithymocyte globulin (ATG) and cyclosporin A (CSA). When used in
      combination these two drugs can improve most patients condition. However, one third of the
      patients who respond to this therapy experience a relapse of SAA. In addition, some patients
      treated with ATG/CSA can later develop other disorders of the blood.

      Recently, researchers have found that another immunosuppressive drug called cyclophosphamide,
      has been successful at treating patients with SAA. In addition, patients treated with
      cyclophosphamide do not experience relapses or develop other disorders of the blood.

      In this study researchers would like to compare the combinations of antithymocyte globulin
      (ATG) and cyclosporin A (CSA) to cyclophosphamide and cyclosporin A (CSA) for the treatment
      of SAA.
    

Detailed description: 
      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.
    

Intervention name(s): antithymocyte globulin; cyclophosphamide; cyclosporine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): antithymocyte globulin; cyclophosphamide; cyclosporine
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Cyclosporins; Antilymphocyte Serum
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Severe Aplastic Anemia; Immunosuppression