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.

Condition	Treatment or Intervention	Phase
Aplastic Anemia Pure Red Cell Aplasia Thrombocytopenic Purpura	Drug: Daclizumab (Zenapax)  Drug: Daclizumab	Phase II

Further Study Details: 

Expected Total Enrollment:  232

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). To test the efficacy of anti-IL-2R mAb, 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; and 3) relapse of severe aplastic anemia; or 4) refractory disease not responding to both horse and rabbit ATG/CsA.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Acquired moderate aplastic anemia. Moderate aplastic anemia is defined as aplastic anemia (hypocellular bone marrow) and no evidence for other disease process and depression of at least two out of three blood counts below the normal values:
- ANC less than or equal to 1200/mm(3)
- platelet count less than or equal to 70,000/mm(3)
- anemia with hemoglobin less than or equal to 8.5 g/dl and absolute reticulocyte count less than or equal to 60,000/mm(3) in transfusion-dependent patients
but not fulfilling the criteria for severe disease defined by depression of two or three of the peripheral counts:
- ANC less than or equal to 500/mm(3)
- platelet count less than or equal to 20,000/mm(3)
- reticulocyte count less than or equal to 50,000/mm(3)
Or
Acquired pure red cell aplasia or Diamond Blackfan anemia requiring RBC transfusions. Pure red cell aplasia is defined by anemia, reticulocytopenia (reticulocyte count less than or equal to 50,000/mm(3) and absent or decreased marrow erythroid precursors.
Diamond Blackfan anemia is defined by anemia, reticulocytopenia (reticulocyte count less than 50,000/mm3 ) and absent or decreased marrow erythroid precursors diagnosed at a very early age
Or
Relapse in patients with severe aplastic anemia after initial hematologic response to ATG/CSA or cyclophosphamide/CSA (usually during taper or after discontinuation of CSA). The criteria for relapsed aplastic anemia are two of the three as follows:
-ANC less than or equal to 1200/mm(3) or
- platelets to less than or equal to 40,000/mm(3) or
- reoccurrence of need for RBC or platelet transfusion
Relapsed patients with an ANC less than or equal to 200/mm(3) are not eligible for this study and will receive standard treatment with ATG/CSA.
OR:
Refractory disease not responding to both horse and rabbit ATG/CsA.
The criteria for refractory disease not responding to horse and rabbit ATG/CsA are two of the three as follows:
ANC less than 1200 /mm3 or
platelets to less than 40,000/mm3 or
recurrence of need for RBC or platelet transfusion
The average of three measurements of blood counts obtained within a 2-week period prior to enrollment into the study will be used to assess study eligibility. Transfusion-independence is not an exclusion criterion. For the purpose of this study, transfusion-dependence will be defined as requirements of at least 2 units RBC or 5 units of platelets per month for a period of 2 months prior to enrollment in the study. This requirement does not apply to patients with relapse of aplastic anemia.
Age greater than or equal to 2 year old.
Weight greater than 12 kg.
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.
Diagnosis of Diamond-Blackfan anemia and availability of a match related transplant donor.
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.
History of malignancy treated with chemotherapy.
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 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.

Maryland
      National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  000029; 00-H-0029
Record last reviewed:  November 24, 2004
Last Updated:  December 4, 2004
Record first received:  January 18, 2000
ClinicalTrials.gov Identifier:  NCT00001962
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08