Clinical Trial: Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment

Brief Summary:

Background:

  • Severe plastic anemia can lead to problems with bone marrow platelet production and result in low blood platelet counts, which require frequent platelet transfusions to improve blood clotting.
  • A standard treatment for SAA involves injections of rabbit-antithymocyte globulin (r-ATG). r-ATG is developed by injecting horses with a type of human white blood cells called thymocytes. The horse's immune system reacts against these cells and makes antibodies that can destroy them. These antibodies are collected and purified to make r-ATG. Horses can also be used for this procedure to make horse-antithymocyte globulin (h-ATG).
  • h-ATG is approved by the Food and Drug Administration for the treatment of aplastic anemia. h-ATG is a standard first-line method to treat aplastic anemia, but researchers do not know how effective it is in patients who were first treated unsuccessfully with r-ATG.

Objectives:

- To evaluate the effectiveness and safety of horse-ATG (with cyclosporine) in increasing blood counts and reducing the need for transfusions in aplastic anemia patients who have failed to respond to prior immunosuppressive treatment with rabbit-ATG and cyclosporine.

Eligibility:

- Patients 2 years of age and older who have consistently low blood platelet counts related to aplastic anemia that has not responded to conventional treatment with rabbit-ATG.

Design:

  • After initial screening, medical history, and blood tests, patients will be admit

    Detailed Summary:

    Severe aplastic anemia (SAA), characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggests that patients with minimal blood count responses to a single course of ATG, even when transfusion independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement.

    The majority of the experience in the US and worldwide has been with horse ATG (h-ATG) plus CsA as initial therapy in SAA. Rabbit ATG (r-ATG) plus CsA has been employed successfully in about 1/3 of cases in those who are refractory to initial h-ATG/CsA (current NHLBI Protocol 03-H-0249). In recent years, h-ATG and r-ATG have been used interchangeably in treatment-naive patients, and initial therapy with r-ATG/CsA is now frequent in the US and the only option in Europe and Japan, where h-ATG is no longer available. An active NHLBI randomized study is comparing the efficacy of h- and r-ATG as initial therapy in SAA, and the results from a recently completed interim analysis suggest that the hematologic response rate ultimately may not be comparable between these two agents (Protocol 06-H-0034). There is no published report on the outcome of repeat immunosuppressive therapy in those patients refractory to initial r-ATG/CsA, and thus the management of these patients is uncertain. We therefore propose this study of h-ATG/CsA in SAA patients who are refractory or have a suboptimal re
    Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

    Current Primary Outcome:

    • Number of Participants With Complete Response at 3 Months. [ Time Frame: 3-months ]

      The primary endpoint was hematologic response at 3 months, defined as no longer meeting criteria for Severe Aplastic Anemia (SAA) defined as bone marrow cellularity of less than 30% and severe pancytopenia with at least two of the following peripheral blood count criteria: (i) absolute neutrophil count less than 0.5×109/L; (ii) absolute reticulocyte count less than 60×109/L; and (iii) platelet count less than 20×109/L.

      A complete response was defined as absolute neutrophil count (ANC) above 1.0×109/L, Hgb > 10 g/dL, and platelet count > 100×109/L.

      A partial response was defined as a hematologic response that was not sufficient for a complete response.

    • Number of Participants With Complete Response at 3 Months. [ Time Frame: 3 months ]

      The primary endpoint was hematologic response at 3 months, defined as no longer meeting criteria for Severe Aplastic Anemia (SAA).

      A complete response was defined as absolute neutrophil count (ANC) above 1.0×109/L, Hgb > 10 g/dL, and platelet count > 100×109/L.

      A partial response was defined as a hematologic response that was not sufficient for a complete response.

      In subjects with a non-robust hematologic response at 3 months, improvement in one or more of the listed peripheral blood parameter (a,b,c) were recorded as a response:

      Original Primary Outcome: Changes absolute neutrophil count, platelet count, reticulocyte count at 3 months.

      Current Secondary Outcome:

      Original Secondary Outcome: Time to relapse, changes in cytogenetics, time to death.

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: July 22, 2009
      Date Started: July 2009
      Date Completion: December 2020
      Last Updated: February 22, 2017
      Last Verified: February 2017