Rituximab to Treat Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia
Condition: Anemia, Aplastic; Red-Cell Aplasia, Pure; Anemia, Diamond-Blackfan
MeSH terms: Anemia; Anemia, Aplastic; Anemia, Diamond-Blackfan; Red-Cell Aplasia, Pure
Intervention: Rituximab
Intervention description: Rituximab (Rituxan) 375mg/m2 intravenous infusion. The infusion will be once every week for a total of 4 doses.
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: rituxan; Immunosuppression; Bone Marrow Failure; Monoclonal Antibody Therapy; Diamond Blackfan Anemia (DBA); T -Cells; B-Cells; Hematopoiesis; Moderate Aplastic Anemia (MAA); Diamond-Blackfan Anemia; DBA; Pure Red Cell Aplasia; PRCA

Summary:

      This study will test whether the immune-suppressing drug rituximab can increase blood counts
      and reduce the need for transfusions in patients with moderate aplastic anemia, pure red cell
      aplasia, or Diamond Blackfan anemia. These are rare and serious blood disorders in which the
      immune system turns against bone marrow cells, causing the bone marrow to stop producing red
      blood cells in patients with pure red cell aplasia and Diamond Blackfan anemia, and red blood
      cells, white blood cells and platelets in patients with aplastic anemia. Rituximab is a
      laboratory-made monoclonal antibody that recognizes and destroys white blood cells called
      lymphocytes that are responsible for destroying bone marrow cells in these diseases. The drug
      is currently approved by the Food and Drug Administration for treating patients with B-cell
      non-Hodgkin lymphoma, a disease of white blood cells.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Diagnosis of acquired moderate aplastic anemia defined as aplastic anemia (hypocellular
        bone marrow) and no evidence for an underlying disease process and depression of at least
        two out of three blood counts below these values:

          -  Absolute neutrophil count (ANC) equal to or less than l200/mm(3)

          -  platelet count equal to or less than 70,000/mm(3)

          -  anemia with hemoglobin equal to or less than 8.5 g/dl or absolute reticulocyte count
             equal to or less than 60,000/mm(3) in transfusion-dependent patients but not
             fulfilling the criteria for severe disease defined by bone marrow cellularity less
             than 30% (excluding lymphocytes) and depression of at least two of the three
             peripheral counts:

          -  ANC equal to or less than 500/ul

          -  platelet count equal to or less than 20,000/ul

          -  reticulocyte count less than 60,000/ul

        Or

        Diagnosis of pure red cell aplasia or Diamond Blackfan anemia requiring red blood cell
        (RBC) transfusions

        Pure red cell aplasia is defined by

          -  anemia,

          -  reticulocytopenia (reticulocyte count equal to or less than 50,000/ mm(3))

          -  and absent or decreased marrow erythroid precursors

        Diamond Blackfan anemia is defined by

          -  anemia,

          -  reticulocytopenia (reticulocyte count equal to or less than 50,000/ mm(3))

          -  and absent or decreased marrow erythroid precursors diagnosed at an early age

        Because this population is prone to dry bone marrow aspirates, subjects from whom
        sufficient bone marrow cannot be collected for the evaluation of cellularity will not be
        excluded provided they meet all other inclusion criteria based on peripheral blood counts.

        Pure Red cell Aplasia and Diamond Blackfan patients must be age greater than or equal to 2
        years old and weight greater than 12 kg; Moderate Aplastic anemia patients must be age
        greater than or equal to 18.

        Refractory to at least 1 course of immunosuppressive therapy or relapsed disease after
        prior immunosuppressive therapy (PRCA/DBA patients only).

        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 of Fanconi's anemia or other congenital bone marrow failure syndromes
        except for DBA

        History of a cytogenetic abnormality indicating myelodysplasia (MDS)

        Active infection not adequately responding to appropriate therapy

        HIV positivity

        Positive anti- hepatitis B core antibody (antiHBc) or HBsAG

        History of clinically significant arrhythmia

        Known anaphylaxis or immunoglobulin E (IgE) mediated hypersensitivity to murine proteins or
        to any component of this product.

        Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
        or metabolic disease of such severity that it would preclude the patient's ability to
        tolerate protocol therapy, or that death within the next month is likely

        Potential subjects with cancer who are on active chemotherapeutic treatment or who take
        drugs with hematological effects will not be eligible.

        History of recent or ongoing B19 parvovirus infection

        Psychiatric, affective, or other disorder that may compromise the ability to give informed
        consent or to cooperate in a research study.

        Pregnancy or lactation or unwillingness to take contraceptives

        Participation in any other investigational drug trial or exposure to other investigational
        agents (other than hematopoietic growth factors) within 30 days of study entry. Use of low
        dose immunosuppressive agents may continue at the PIs discretion provided that the patient
        has been taking this drug for at least 3 months.