Protocol Number: 00-H-0029

Title:

A Pilot Study of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) in Patients with Moderate Aplastic Anemia, Pure Red Cell Aplasia, or Diamond Blackfan Anemia

Number:

00-H-0029

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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility 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

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.

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.

Special Instructions:

Currently Not Provided

Keywords:

Immunosuppression

T-cells

Hematopoiesis

Monoclonal Antibody Therapy

Immunosuppressive Therapy

Recruitment Keyword(s):

Aplastic Anemia

Condition(s):

Aplastic Anemia

Pure Red Cell Aplasia

Diamond Blackfan Anemia

Investigational Drug(s):

Daclizumab (Zenapax)

Investigational Device(s):

None

Intervention(s):

Drug: Daclizumab

Drug: Daclizumab (Zenapax)

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

The treatment of severe aplastic anemia

The pathophysiology of acquired aplastic anemia

Bone marrow and peripheral blood phynotype in patients with bone marrow failure

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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