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
Many bone marrow failure syndromes in humans are now recognized to result from immunological
mechanisms. These diseases include aplastic anemia; single hematopoietic lineage failures
such as pure red cell aplasia, Diamond Blackfan Anemia, agranulocytosis, and amegakaryocytic
thrombocytopenic purpura; and some types of myelodysplasia. Patients with these conditions,
who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or
combination, have been shown to respond to a wide variety of immunosuppressive agents,
ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG).
However, except for severe aplastic anemia, which has been shown to be appropriately treated
with either bone marrow transplantation or a combination of ATG and CSA, single agents or
regimens have usually not been applied systematically to other immune-mediated hematologic
diseases. In an effort to discover other and especially less toxic treatments for
immunologically-mediated bone marrow diseases, we seek to apply a new therapy, a humanized
anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb ), to a subset of patients with
bone marrow failure. Anti-IL-2R mAb acts against activated lymphocytes, thus sharing an
important mechanism of action with ATG. However, the mAb is much less toxic than ATG and
may be administered to outpatients at relatively infrequent intervals (every 2 weeks).
The primary objective is to test the efficacy of anti-IL-2R mAb (daclizumab), we propose to
treat four groups of patients: 1) moderate aplastic anemia, 2) single lineage failure states
including pure red cell aplasia or Diamond Blackfan anemia, 3) relapse of severe aplastic
anemia and 4) refractory severe aplastic anemia not responding to both horse and rabbit
ATG/CsA. Subjects will receive daclizumab once every other week for a total of 5 doses.
Patients relapsing after response to initial treatment may be treated with 2 additional
courses of daclizumab. In November 2005, the relapsed and refractory severe aplastic anemia
arms were closed by the DSMB for lack of efficacy. In October 2008, the moderate aplastic
anemia arm was closed by the DSMB when the data was determined sufficient for making
statistical inferences regarding the original hypotheses. In October 2008, accrual to the
Diamond Blackfan anemia arm was closed by the DSMB for lack of accrual.
The Primary endpoint is hematologic response at 3 months. Secondary endpoints include
transfusion dependence, overall survival, life threatening toxicity, transformation-free
survival, and response duration.
1. Acquired pure red cell aplasia requiring RBC transfusions defined by
- 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 (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.
Current diagnosis or past history of myelodysplastic syndrome or Fanconi's anemia.
Known allergy to E.coli-derived products.
Persistant 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 NY 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.