A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure

NCT00001962 | Terminated Phase 2 Results DMC

• 2 other identifiers: 00002900-H-0029
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aplastic Anemia; Pure Red Cell Aplasia; Diamond Blackfan Anemia

Keywords

Immunosuppression; T-cells; Hematopoiesis; Monoclonal Antibody Therapy; Immunosuppressive Therapy; Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematologic Response Following Daclizumab in Patients With Moderate Aplastic Anemia (MAA) and Pure Red Cell Aplasia (PRCA).

  Number of participants with hematologic response at 3 months following Daclizumab, 1 mg/kg, will be given for a total of 5 intravenous infusions to subjects diagnosed with moderate aplastic anemia (MAA), pure red cell aplasia (PRCA), Diamond Blackfan anemia (DBA), relapse and refractory severe aplastic anemia (SAA) will receive treatment. A complete hematologic response will be considered an achievement of normal blood counts. A partial response was defined as any response less than a complete response. The primary endpoint was a hematologic response in at least one affected peripheral blood count parameter, as determined by 3 separate measurements in the first 12 weeks after completion of the infusion.

  3 months

Secondary Outcomes (2)

• Number of Participants That no Longer Required Blood Transfusion

  5 years

• Overall Survival

  5 years

Study Arms (1)

Daclizumab in participants with a bone marrow failure syndrome

EXPERIMENTAL

daclizumab, 1 mg/kg, will be given for a total of 5 intravenous infusions. These subjects may be diagnosed with moderate aplastic anemia, pure red cell aplasia, Diamond Blackfan anemia, relapse and refractory severe aplastic anemia will receive treatment. The subjects will be seen and receive the daclizumab infusion biweekly during the treatment period.

Drug: Daclizumab

Interventions

Daclizumab DRUG

Daclizumab, 1mg/kg, every 2 weeks for a total of 5 infusions.

Also known as: Zenapax

Daclizumab in participants with a bone marrow failure syndrome

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Age greater than or equal to 2 years 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.

  PMID: 7780125 BACKGROUND

• Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.

  PMID: 9134878 BACKGROUND

• Maciejewski JP, Hibbs JR, Anderson S, Katevas P, Young NS. Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure. Exp Hematol. 1994 Oct;22(11):1102-10.

  PMID: 7925777 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic; Red-Cell Aplasia, Pure; Anemia, Diamond-Blackfan

Interventions

Daclizumab

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Hypoplastic, Congenital; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Neal Young MD
• Organization: NIH National Heart, Lung and Blood Institute

youngns@nhlbi.nih.gov

301-496-5093

Study Officials

• Neal Young, MD

  NIH National Heart, Lung, and Blood Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2000
• First Posted: January 19, 2000
• Study Start: November 1, 1999
• Primary Completion: August 1, 2009
• Study Completion: September 1, 2010
• Last Updated: July 9, 2021
• Results First Posted: May 14, 2015

Record last verified: 2015-04

Locations

US (1)