Completed

Treatment of Severe Aplastic Anemia With Combined Immunosuppression: Antithymocyte Globulin (ATG) and Cyclosporine A (CSA), and Mycophenolate Mofetil (MMF)

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What is being tested

Cyclosporine A

+ ATG

+ MMF

Drug
Who is being recruted

Anemia+3

+ Bone Marrow Diseases

+ Hematologic Diseases

From 1 to 99 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: March 2000
See protocol details

Summary

Principal SponsorNational Heart, Lung, and Blood Institute (NHLBI)
Last updated: March 16, 2021
Sourced from a government-validated database.Claim as a partner

Study start date: March 17, 2000

Actual date on which the first participant was enrolled.

Severe acquired aplastic anemia (SAA) has a poor prognosis if untreated. Bone marrow transplantation is available to only a minority of patients due to lack of a matched sibling donor, advanced age of the patient, or cost. Clinical studies at NIH and elsewhere have demonstrated excellent response rates and improved survival with immunosuppressive treatments. Laboratory data implicate underlying cytotoxic T-lymphocyte-mediated suppression of hematopoiesis as the likely proximal cause of disease in most patients. In earlier clinical protocols we treated SAA with cyclosporine A (CSA) (86-H-0007), antithymocyte globulin (ATG) (87-H-0124), and combined ATG and CSA (90-H-0146). While intensive immunosuppression is most effective, relapse is common and some patients also develop second hematologic complications like myelodysplasia. In this protocol, we modify our regimen by delaying the introduction of cyclosporine to promote ATG tolerizing effects and adding mycophenolate mofetil (MMF), a new agent that, like ATG may be relatively specific for activated lymphocytes, in an effort to reduce the high relapse rate.

NCT00001964
Principal SponsorNational Heart, Lung, and Blood Institute (NHLBI)
Last updated: March 16, 2021
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

104 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

From 1 to 99 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

AnemiaBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Failure DisordersAnemia, Aplastic

Criteria

INCLUSION CRITERIA: Only patients with SAA will be admitted, defined as: Bone marrow cellularity less than 30%. At least two of the following blood count findings: absolute granulocyte count less than 500/mm(3); platelet count less than 20,000/mm(3); reticulocyte count less than 60,000/mm(3). Age greater than or equal to 1 years. Weight greater than 12 kg. EXCLUSION CRITERIA: Serum creatinine greater than 2 mg/dl or estimated creatinine clearance less than 40 ml/min. Underlying carcinoma, recent history of radiation or chemotherapy. Current pregnancy or unwillingness to be treated with oral contraceptives. Inability to comprehend the investigational nature of the study. Moribund status or concurrent hepatic, renal, cardiac, neurologic, or metabolic disease of such severity that death within 7 to 10 days is likely. Evidence of other etiology than AA for bone marrow failure, including positive clastogenic stress cytogenetic assay for Fanconi anemia and marrow chromosome abnormalities typical of myelodysplasia.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

2 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
ATG 40 mg/kg/d for 4 d; CsA 2 weeks after at 12 mg/kg/d for 6 months. MMF starting on first day of ATG at 600 mg/m2 twice daily for 18 months

Group II

Experimental
ATG at 40 mg/kg/day for 4 days; MMF at 600 mg/m2 twice daily for 18 months and CsA at 12 mg/kg/day for 6 months starting 2 weeks after ATG and MMF

Study Objectives

Primary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, United StatesOpen National Institutes of Health Clinical Center, 9000 Rockville Pike in Google Maps
CompletedOne Study Center