Complement Inhibition Using Eculizumab to Overcome Platelet Transfusion Refractoriness in Patients With Severe Thrombocytopenia
Condition: Thrombocytopenia; Alloimmune Platelet Refractoriness
MeSH terms: Thrombocytopenia
Intervention: Eculizumab
Intervention description: 300 mg single-use vials
Intervention MeSH terms: Eculizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Complement Inhibition; Platelet Refractoriness; Eculizumab

Summary:

      Background:

      - Platelets are tiny cells in the blood that help stop bleeding. Thrombocytopenia happens
      when people do not have enough normal platelets. Getting a transfusion of another person s
      platelets can help stop too much bleeding. But because these cells are from other people, the
      body may reject them,putting them at risk for serious bleeding complications. This conditions
      is called alloimmune platelet refractoriness . There are evidence that in many patients,
      platelet counts fail to increase after a platelet transfusion because the transfused
      platelets are destroyed by the body s defence soldier, called complement . Researchers want
      to see if a drug, that inhibits complement, can help increase platelet levels and reduce
      bleeding

      Objectives:

      - To see if eculizumab increases platelet levels more after a transfusion. To see if it
      reduces the chance of bleeding too much.

      Eligibility:

      - Adults 18-75 years old who have thrombocytopenia and alloimmune platelet refractoriness.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood tests.

        -  Participants will have the procedures listed below. They can have them while they are in
           the hospital. Or they can go to the outpatient clinic for them. Each visit may take up
           to 3 hours.

        -  Participants will get a meningitis vaccine if needed. Then they will get the study drug
           as an infusion.

        -  Participants will have a platelet transfusion. Their blood will be drawn every 24 hours
           until the platelet count is less than 10,000 per 1 microliter of blood.

        -  They will take antibiotics for 14 days.

        -  Participants will have a checkup and blood drawn twice a week for 2 weeks. They will get
           more transfusions if needed.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Ages 18-75 years inclusive.

          -  Ability to comprehend the investigational nature of the study and provide informed
             consent.

          -  Thrombocytopenia (due to congenital causes, bone marrow failure, hematologic
             malignancies, and treatment related), defined as <10k/uL without bleeding or <30K/uL
             with evidence of life threatening bleeding (intracranial hemorrhage, GI bleeding,
             pulmonary hemorrhage, uncontrolled epistaxis, hematuria).

          -  Diagnosed with immune platelet refractoriness, characterized by all of the following:

               -  Lack of adequate post-transfusion platelet count increment, defined by, CCI
                  <7500/ul at 10-60 min, and CCI <5000/ul at 18-24 hrs (in those who had a CCI at
                  10-60 min greater than or equal to 5000/microl)after at least 2 consecutive
                  transfusions.

               -  Presence of anti-HLA class A and/or B antibody.

        EXCLUSION CRITERIA:

          -  Active meningococcal infection.

          -  Severe psychiatric illness. Mental deficiency sufficiently severe as to make making
             informed consent impossible.

          -  Positive pregnancy test for women of childbearing age within 1 week.

          -  HIV positive test within 3 months

          -  Paroxysmal Nocturnal Hemoglobinuria (PNH) disease with evidence of intravascular
             hemolysis.

          -  Presence ITP/autoimmune thrombocytopenia

          -  Immune platelet refractoriness responsive to treatment with IVIG

        RE-ENROLLMENT CRITERIA:

          -  Meet response criteria to the initial treatment or second treatment

          -  Meets all initial inclusion/exclusion criteria