Combination Therapy of Severe Aplastic Anemia

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-03-17

Study Completion Date

2015-05-12

Brief Summary

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This study will test the safety and effectiveness of a combination of three drugs in treating severe aplastic anemia and preventing its recurrence. Two drugs used in this trial ATG and cyclosporine are standard combination therapy for aplastic anemia. This study will try to improve this therapy in three ways: 1) by altering the drug regimen to allow the drugs to work better; 2) by reducing the risk of kidney damage; and 3) by adding a third drug mycophenolate mofetil to try to prevent disease relapse.

Patients with severe aplastic anemia who do not have a suitable bone marrow donor or who decline bone marrow transplantation may participate in this study. Patients will have a skin test for ATG allergy, chest X-ray, blood test, and bone marrow aspiration before treatment begins. ATG will then be started, infused through a vein continuously for 4 days. Ten days after ATG is stopped, cyclosporine treatment will begin, taken twice a day by mouth in either liquid or capsule form and will continue for 6 months. Also, in the first 2 weeks of treatment, patients will be given a full dose of corticosteroid (prednisone) to prevent serum sickness that could develop as a side effect of ATG therapy. The dosage will be decreased after that. Mycophenolate will be started at the same time as ATG, in two daily doses by mouth, and will continue for 18 months.

Patients will be hospitalized at the beginning of the study. During this time, blood will be drawn at 3-week intervals and a bone marrow examination will be repeated 3 months after treatment has begun. Additional tests, including X-rays may be required. After hospital discharge, patients will be followed on an outpatient basis at 3-month intervals. The patients own physician will perform blood tests weekly and kidney and liver function tests every 2 weeks during cyclosporine therapy. Transfusions may be required initially.

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Detailed Description

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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.

Conditions

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Severe Aplastic Anemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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single arm

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 Type EXPERIMENTAL

Cyclosporine A

Intervention Type DRUG

Cyclosporine A

ATG

Intervention Type DRUG

ATG

MMF

Intervention Type DRUG

MMF

single arm 2

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

Group Type EXPERIMENTAL

Cyclosporine A

Intervention Type DRUG

Cyclosporine A

ATG

Intervention Type DRUG

ATG

MMF

Intervention Type DRUG

MMF

Interventions

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Cyclosporine A

Intervention Type DRUG

ATG

Intervention Type DRUG

MMF

Intervention Type DRUG

Eligibility Criteria

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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.

Minimum Eligible Age

1 Year

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No