A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
Condition: Aplastic Anemia; Pure Red Cell Aplasia; Diamond Blackfan Anemia
MeSH terms: Anemia; Anemia, Aplastic; Anemia, Diamond-Blackfan; Red-Cell Aplasia, Pure
Intervention: Daclizumab
Intervention description: Daclizumab, 1mg/kg, every 2 weeks for a total of 5 infusions.
Intervention MeSH terms: Daclizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Immunosuppression; T-cells; Hematopoiesis; Monoclonal Antibody Therapy; Immunosuppressive Therapy; Aplastic Anemia

Summary:

      Participants in this study are suffering from rare and serious blood disorders. In aplastic
      anemia, the bone marrow stops producing red blood cells, platelets, and white blood cells. In
      pure red cell aplasia, the bone marrow stops producing red cells, and in amegakaryocytic
      thrombocytopenic purpura, the bone marrow stops producing platelets.

      Current treatment approaches for these disorders include bone marrow transplant and/or
      immunosuppression. However, bone marrow transplant is not always possible, and
      immunosuppression has serious side effects.

      This study will investigate whether daclizumab can be used to treat these disorders.
      Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor
      on immune cells. It has been used successfully in many transplant patients to reduce the rate
      of organ rejection.

      Participants will undergo a complete history and physical examination. A bone marrow
      aspiration and biopsy will be performed to confirm the type of bone marrow failure. About 5
      tablespoons of blood will be drawn for baseline tests and research purposes. Daclizumab will
      be administered every 2 weeks by vein in a 30-minute infusion. The first dose will be given
      at NIH and the next four may be given at NIH or by the participant's primary hematologist.
      The treatment will last 8 weeks. Participants must also see their referring physician or NIH
      physicians every 2 weeks for blood counts. In the fourth and eighth weeks of the study and at
      the 3-month follow-up visit, 2 tablespoons of blood will be drawn at NIH. At the 1-month
      follow-up visit to NIH, 5 tablespoons of blood will be drawn and another bone marrow
      aspiration and biopsy performed.

      Risks from bone marrow aspiration and biopsy and blood draws include discomfort. Daclizumab
      is usually well-tolerated; however, it may weaken immunity against certain bacteria and
      viruses.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Acquired pure red cell aplasia requiring red blood cell (RBC) transfusions defined by

               -  anemia,

               -  reticulocytopenia (reticulocyte count less than or equal to 50,000/mm(3))

               -  and absent or decreased marrow erythroid precursors

             Acquired aplastic anemia of moderate severity (In October 2008, this arm was closed by
             the DSMB when the data was determined sufficient for making statistical inferences
             regarding the original hypotheses.

             Diamond Blackfan Anemia (DBA) (In October 2008, accrual of DBAs was closed by the DSMB
             for lack of accrual)

             Relapsed patients with severe aplastic anemia (In November 2005 this arm was closed by
             the DSMB for lack of efficacy)

             Refractory disease not responding to both horse and rabbit ATG/CsA (In November 2005
             this arm was closed for lack of efficacy)

          2. Age greater than or equal to 2 years old

          3. Weight greater than 12 kg

          4. Patients or their parent(s)/responsible guardian(s) must be able to comprehend and be
             willing to sign an informed consent.

        EXCLUSION CRITERIA:

        Current diagnosis or past history of myelodysplastic syndrome or Fanconi's anemia.

        Known allergy to E.coli-derived products.

        Persistent B19 parvovirus infection.

        Evidence of uncontrolled infection.

        Chronic or current clinically significant infection, including HIV positivity or hepatitis
        B and C virus infection.

        Significant other diseases, congestive heart failure (greater than New York Class II),
        poorly controlled diabetes mellitus, uncontrolled cardiac arrhythmias.

        Subjects with cancer who are on active chemotherapeutic treatment or who take drugs with
        hematological effects will not be eligible

        A moribund status or concurrent hepatic, renal, cardiac, metabolic disease of such severity
        that death within 1-4 weeks from initiation of therapy is likely.

        Recent major surgery.

        Treatment with an investigational agent other than hematopoietic growth factors within 4
        weeks of study entry.

        Psychiatric, affective, or other disorder that may compromise the ability to give informed
        consent or to cooperate in a research study.

        Pregnancy or lactation.