- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00001626
Comparing Therapies for the Treatment of Severe Aplastic Anemia
A Randomized Trial of Antithymocyte Globulin and Cyclosporine Versus Cyclophosphamide and Cyclosporine in the Treatment of Severe Aplastic Anemia
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
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).
EXCLUSION CRITERIA:
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A
D1-4 cyclophosphamide 50 mg/kg IV, then cyclosporine starting on d14 at 12 mg/kg/d for 6 months
|
cyclophosphamide
cyclosporine
|
Experimental: B
ATG at 40 mg/kg/d for 4 days then cyclosporine at 12 mg /kg/d for 6 months
|
cyclosporine
antithymocyte globulin
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Compare the sustained response proportions among patients with SAA treated with immunosuppressive therapy with either ATG/CSA or high dose cyclophosphamide and CSA.
Time Frame: 12 weeks.
|
12 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall and event-free survival.
Time Frame: 12 months
|
12 months
|
Response duration. Evolution to PNH, myelodysplasia, and active leukemia.
Time Frame: 12 months
|
12 months
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Bone Marrow Diseases
- Hematologic Diseases
- Bone Marrow Failure Disorders
- Anemia
- Anemia, Aplastic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Antifungal Agents
- Calcineurin Inhibitors
- Cyclophosphamide
- Antilymphocyte Serum
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 970117
- 97-H-0117
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Severe Aplastic Anemia (SAA)
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National Institutes of Health Clinical Center (CC)National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia (SAA)United States
-
AmgenWithdrawn
-
Novartis PharmaceuticalsActive, not recruitingSevere Aplastic Anemia (SAA)Japan, Korea, Republic of, China, Taiwan
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia (SAA)United States
-
Regeneron PharmaceuticalsRecruitingSevere Aplastic Anemia (SAA)United States, France, Korea, Republic of, United Kingdom
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia (SAA) | Myelodysplastic Syndrome (MDS) With Refractory Anemia (RA)United States
-
University of UtahNovartisCompletedSevere Aplastic Anemia | Moderate Aplastic Anemia | Very Severe Aplastic AnemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingRecurrent Severe Aplastic Anemia | Refractory Severe Aplastic AnemiaUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedSevere Aplastic Anemia, Refractory | Severe Aplastic Anemia, RelapseUnited States
-
Assistance Publique - Hôpitaux de ParisNot yet recruitingSevere Aplastic Anemia | Idiopathic Aplastic Anemia | Moderate Aplastic Anemia Requiring Transfusions
Clinical Trials on cyclophosphamide
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Children's Hospital Los AngelesLucile Packard Children's HospitalTerminatedMetabolic Diseases | Stem Cell Transplantation | Chronic Granulomatous Disease | Bone Marrow Transplantation | Thalassemia | Wiskott-Aldrich Syndrome | Genetic Diseases | Peripheral Blood Stem Cell Transplantation | Pediatrics | Diamond-Blackfan Anemia | Allogeneic Transplantation | Combined Immune Deficiency | X-linked Lymphoproliferative Disease
-
Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedAnemia, AplasticUnited States
-
Columbia UniversityUnknownSevere Combined Immunodeficiency | Fanconi Anemia | Bone Marrow Failure | OsteopetrosisUnited States
-
National Cancer Institute, NaplesImmatics Biotechnologies GmbH; CureVac; European Commission -FP7-Health-2013-Innovation-1CompletedHepatocellular CarcinomaBelgium, Germany, Italy, Spain, United Kingdom
-
Mahidol UniversityTerminatedRenal Insufficiency | InfectionThailand
-
Centre Oscar LambretCompleted
-
Eisai Inc.CompletedBreast Cancer | Ovarian Cancer | Prostate Cancer | Colon Cancer | Renal CancerUnited States
-
Baylor Research InstituteCompletedMalignant Melanoma Stage IVUnited States
-
University of Turin, ItalyUnknown
-
Merck KGaA, Darmstadt, GermanyCompleted