Treatment of Autoimmune Thrombocytopenia (AITP)
Condition: Autoimmune Disease; Autoimmune Hemolytic Anemia; Thrombocytopenia
MeSH terms: Thrombocytopenia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Purpura, Thrombocytopenic, Idiopathic; Autoimmune Diseases; Hemolysis
Study type: Interventional
Phase: Phase 1

Summary: 
      Platelets are particles found along with red and white blood cells in the blood that play a
      role in the process of blood clotting. Disorders affecting the platelets can lower the amount
      of platelets in the blood and put patients at risk of bleeding. The condition of low
      platelets is referred to as thrombocytopenia.

      Thrombocytopenia can be associated with a variety of diseases including cancer, leukemia,
      tuberculosis, or as a result of an autoimmune reaction. Autoimmune reactions are disorders in
      which the normal immune system begins attacking itself. Autoimmune thrombocytopenia (AITP) is
      a disorder of low blood platelet counts in which platelets are destroyed by antibodies
      produced by the immune system.

      Unfortunately, many patients with AITP do not respond to standard treatments for
      thrombocytopenia. Cyclophosphamide is a drug that works to suppress the activity of the
      immune system. Researchers believe that combining this drug with transplanted rescued blood
      stem cells may provide effective treatment for AITP.

      The purpose of this study is to explore the affordability and safety of this therapy for the
      treatment of AITP. The effectiveness of the therapy will be measured by the number of
      patients whose platelet levels rise greater than 100,000/m3.

      If this treatment approach appears affordable, this study will form the basis for a larger
      study to compare alternate treatment approaches.
    

Detailed description: 
      Autoimmune Thrombocytopenia (AITP) is a disorder of low blood platelet counts in which
      platelet destruction is caused by antiplatelet autoantibodies. A large proportion of patients
      with chronic AITP are refractory to standard therapies including corticosteroids, immune
      globulin and splenectomy. Cyclophosphamide is a cytotoxic immunosuppressive agent which may
      induce durable remissions of refractory autoimmune diseases. High-dose cyclophosphamide with
      peripheral blood stem cell (PBPC) rescue has been proposed as a potential definitive therapy
      for AITP; however, the infusion of autoreactive lymphocytes could result in relapse. The use
      of PBPC depleted of T-lymphocytes could circumvent this limitation.

      The purpose of this phase I/II study is to explore the feasibility and safety of this
      approach, and to seek preliminary evidence of effectiveness, of using high-dose
      cyclophosphamide (50 mg/kg/day x 4) followed by infusion of autologous PBPC enriched for
      CD34+ cells (concomitantly depleted of CD3+ cells) for the treatment of patients with
      refractory AITP. Safety/feasibility parameters to be examined will include the ability to
      mobilize, harvest and purify sufficient PBPC to yield greater than 2 x 10(6) CD34+ cells/kg;
      symptomatic acceptability and hematologic toxicities of the mobilization regimen (filgrastim
      10 micrograms/kg/day IV); tolerability of the leukapheresis procedure, including the central
      line placement and maintenance; depth and duration of blood cell nadirs following
      chemotherapy; peritransplant bleeding episodes and transfusion requirements; episodes of
      febrile neutropenia, culture-proven infections and antibiotic usage. Effectiveness will be
      gauged by the rapidity and number of patients to achieve complete remission (platelet count
      greater than 100,000/mm(3) and partial remission (platelet count greater than 50,000/mm(3) or
      doubling of the platelet count with resolution of bleeding episodes). Ancillary evidence of
      therapeutic effect will be sought by examining changes in titers of platelet surface
      glycoprotein antibodies. In addition, alterations in T-lymphocyte subsets will be examined by
      flow cytometry. If this treatment approach appears feasible, this study will form the basis
      for a larger trial to compare alternate treatment approaches.
    

Intervention name(s): Isolex 300i
Intervention type(s): Device
Allocation: Non-Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immunosuppression; Thrombocytopenia; Autoimmune Disease; Evan's Syndrome; Autoimmune Hemolytic Anemia; Episodic Bleeding