Comparing Therapies for the Treatment of Severe Aplastic Anemia

NCT00001626 | Completed Phase 2

• 2 other identifiers: 97011797-H-0117
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Severe Aplastic Anemia (SAA) is a rare and very serious blood disorder in which the bone marrow stops producing the cells which make up blood; red blood cells, white blood cells, and platelets. Researchers believe this is caused by an autoimmune reaction, a condition in which the natural defense system of the body begins attacking itself. In SAA the immune system begins attacking the bone marrow. Red blood cells are responsible for carrying oxygen to all of the organ systems in the body, and low numbers (anemia) can cause difficulty breathing and fatigue. Platelets are responsible for normal blood clotting and low numbers can result in easy bruising and bleeding which can be deadly. White blood cells are responsible for fighting infections, and low numbers of these can lead to frequent infections, the most common cause of death in patients with aplastic anemia. SAA can be treated by bone marrow transplant (BMT) or by drugs designed to slow down the immune system (immunosuppressants). BMT can be successful, but it requires a donor with matched bone marrow, making this therapy available only to a few patients. BMT with unmatched bone marrow can fail and cause dangerous side effects. Presently, the two drugs used to treat SAA by slowing down the immune system (immunosuppression) are antithymocyte globulin (ATG) and cyclosporin A (CSA). When used in combination these two drugs can improve most patients condition. However, one third of the patients who respond to this therapy experience a relapse of SAA. In addition, some patients treated with ATG/CSA can later develop other disorders of the blood. Recently, researchers have found that another immunosuppressive drug called cyclophosphamide, has been successful at treating patients with SAA. In addition, patients treated with cyclophosphamide do not experience relapses or develop other disorders of the blood. In this study researchers would like to compare the combinations of antithymocyte globulin (ATG) and cyclosporin A (CSA) to cyclophosphamide and cyclosporin A (CSA) for the treatment of SAA.

Conditions

Severe Aplastic Anemia (SAA)

Keywords

Severe Aplastic Anemia; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Compare the sustained response proportions among patients with SAA treated with immunosuppressive therapy with either ATG/CSA or high dose cyclophosphamide and CSA.

  12 weeks.

Secondary Outcomes (2)

• Overall and event-free survival.

  12 months

• Response duration. Evolution to PNH, myelodysplasia, and active leukemia.

  12 months

Study Arms (2)

A

EXPERIMENTAL

D1-4 cyclophosphamide 50 mg/kg IV, then cyclosporine starting on d14 at 12 mg/kg/d for 6 months

Drug: cyclophosphamide; Drug: cyclosporine

B

EXPERIMENTAL

ATG at 40 mg/kg/d for 4 days then cyclosporine at 12 mg /kg/d for 6 months

Drug: antithymocyte globulin; Drug: cyclosporine

Interventions

antithymocyte globulin DRUG

antithymocyte globulin

B

cyclophosphamide DRUG

cyclophosphamide

A

cyclosporine DRUG

cyclosporine

A; B

Eligibility Criteria

• Age: 15 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe aplastic anemia confirmed at NIH by:
• Bone marrow cellularity less than thirty percent (excluding lymphocytes).
• At least two of the following:
• Absolute neutrophil count less that 500/mm(3);
• Platelet count less than 20,000/mm(3);
• Reticulocyte count less than 60,000/mm(3).

You may not qualify if:

• Serum creatinine greater than to 2.5 mg/dl.
• Cardiac ejection fraction less than 45% by MUGA.
• Underlying carcinoma (except local cervical, basal cell, squamous cell or melanoma).
• Current pregnancy or unwilling to take oral contraceptives.
• Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes.
• Evidence of a clonal disorder on cytogenetics.
• HIV positivity.
• Inability to understand the investigational nature of the study.
• Patients who are moribund or have hepatic, renal, cardiac, metabolic or other concurrent diseases of such severity that death within 7-10 days is likely.
• Previous treatment with ATG, or cyclophosphamide.

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 Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Antilymphocyte Serum; Cyclophosphamide; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Study Officials

• Neal S Young, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: June 2, 1997
• Primary Completion: February 20, 2001
• Study Completion: March 3, 2008
• Last Updated: September 22, 2020

Record last verified: 2020-09

Locations

US (1)