Aplastic AnemiaPhase 2NCT00005935
Mycophenolate Mofetil and Cyclosporine to Treat Relapsing Aplastic Anemia
A Phase 2 study testing Mycophenolate mofetil and Cyclosporine in people with Aplastic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of a new drug combination for treating patients with severe aplastic anemia. Patients with aplastic anemia produce too few blood cells, causing fatigue, easy bruising and bleeding, and susceptibility to infections. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Mycophenolate mofetil and Cyclosporine
- How many people
- 130 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2000to Mar 2002
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Subjects with a history of severe aplastic anemia successfully treated by immunosuppression will be included.
Subjects with relapse, as defined above by either return of blood counts to satisfy criteria for severity or consistently declining blood counts will be included.
Subjects age 4 and above will be included.
Subjects with the presence of a medical or surgical condition making survival for at least 3 months unlikely will be excluded.
Subjects with inability to confer informed consent or assent, in the case of a child, either written or verbal, will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized Trial for the Treatment of Relapsing Aplastic Anemia With Mycophenolate Mofetil (MMF) and Cyclosporine (CSA)
This study will examine the safety and effectiveness of a new drug combination for treating patients with severe aplastic anemia. Patients with aplastic anemia produce too few blood cells, causing fatigue, easy bruising and bleeding, and susceptibility to infections. In many cases, the very low blood counts result from an autoimmune process-that is, the patient's own immune system suppresses production of blood cells by the bone marrow. Although immune-suppressing drugs, such as cyclosporine, can restore normal cell counts, many patients have disease relapses. These patients require long-term therapy with cyclosporine, which can cause harmful side effects. This study will examine whether a lower dose of cyclosporine given together with mycophenolate mofetil (MMF) can maintain blood counts as effectively as full-dose cyclosporine treatment, and whether MMF alone can reduce the chances of future relapses.
Patients 4 years of age and older with severe aplastic anemia who have relapsed after immune suppressing therapy may be eligible for this study. Participants will be randomly assigned to receive either standard cyclosporine therapy or experimental therapy with cyclosporine and MMF.
Read more
Patients receiving standard cyclosporine therapy will receive a full dose of the drug for at least 3 months. Those taking both cyclosporine and MMF will take MMF plus half-dose cyclosporine for 3 months and continue MMF for an additional 6 months. Both drugs are taken twice a day by mouth. All patients will have about 120 milliliters (4 ounces) of blood drawn at the beginning of the study to evaluate immune system activity and bone marrow function, and to look for genetic material of certain viruses. Bone marrow aspirations and biopsies will be done at the beginning of the study, and at 6 and 12 months. For these tests, the area of the hip is anesthetized and a special needle is used to draw bone marrow from the hipbone.
The patient's local doctor will be asked to do blood tests for chemistries, liver function and cyclosporine levels weekly for the first month and then every other week. Patients will return to NIH for evaluations 3, 6 and 12 months after treatment and then once a year. About 100 ml (7 tablespoons) of blood will be drawn at each visit.
Read the detailed description
Aplastic anemia is characterized by trilineage hematopoietic failure with an apparently empty bone marrow. While the precise mechanism of disease has yet to be elucidated, much evidence indicates an immunologically mediated pathophysiology. Clinical trials have shown that approximately 75-80% of patients who are treated with immunosuppressive drugs, especially the combination of antithymocyte globulin (ATG) and cyclosporine (CSA), demonstrate a return of hematopoieses and improved blood counts. This therapy now is considered standard care for the treatment of aplastic anemia in all patients who lack a histocompatibility antigen-matched sibling donor and also in older patients regardless of donor status. However, with longer length of evaluation of patients after initial treatment, it is becoming increasingly clear that a substantial proportion will suffer relapse of pancytopenia. ATG and CSA do not appear to cure the disease in these patients but only disrupt a chronic autoimmune process. Recent data from our own series of patients treated with ATG and CSA, and studies of European patients who are treated with antilymphocyte globulin (ALG) and CSA, indicate that approximately 1/3 of responding patients will relapse and require treatment within 1-2 years of discontinuation of CSA. About 15% of patients become dependent on continued CSA administration in order to maintain blood counts. Chronic CSA toxicities include increased susceptibility to infections, hypertension, and irreversible renal damage, as well as hypertrichosis, hyperaesthesias, gingival hyperplasia, headaches, tremors, and other troubling complaints; there is also a possible increased risk of late malignant diseases. Therefore, a major priority in clinical research in aplastic anemia is the development of strategies to produce more durable responses, as well as to identify immunosuppressive agents that can be used as effectively and with fewer side affects than cyclosporine. Mycophenolate mofetil (MMF) is a novel immunosuppressive drug with proven efficacy in the treatment of graft rejection in renal transplantation. MMF has a different toxicity profile from cyclosporine, and specifically does not damage the kidneys. In this study, we will randomize patients who are judged to have relapsed to receive either standard treatment with full dose cyclosporine or half dose cyclosporine combined with MMF. We anticipate that the combination of cyclosporine with MMF will be as effective as conventional high dose cyclosporine for the purpose of treating relapse of aplastic anemia and would provide a less toxic regimen for long-term treatment of this disease.
- Conditions
- Aplastic Anemia
- Being tested
- Mycophenolate mofetil, Cyclosporine
- Keywords
- Immunosuppression, T Cells, Autoimmunity, Bone Marrow Failure, Hematopoiesis, Relapsing Aplastic Anemia
- Medical subject headings
- Anemia, Aplastic, Autoimmune Diseases, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2000 (estimated)
- Study startJun 2000
- Study completionMar 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 130 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005935
- Sponsor's protocol ID
- 000157
- Other IDs
- 00-H-0157
- Status last verified
- Mar 2002
- First submitted
- 6 Jul 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
PubMed 7780125Young NS. Autoimmunity and its treatment in aplastic anemia. Ann Intern Med. 1997 Jan 15;126(2):166-8. doi: 10.7326/0003-4819-126-2-199701150-00014. No abstract available.
PubMed 9005753Rosenfeld SJ, Kimball J, Vining D, Young NS. Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood. 1995 Jun 1;85(11):3058-65.
PubMed 7756640
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial for the Treatment of Relapsing Aplastic Anemia With Mycophenolate Mofetil (MMF) and Cyclosporine (CSA)
- ClinicalTrials.gov ID
- NCT00005935
- Acronym / sponsor ID
- 000157
- Conditions
- Aplastic Anemia
- Keywords
- Immunosuppression, T Cells, Autoimmunity, Bone Marrow Failure, Hematopoiesis, Relapsing Aplastic Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jun 2000
- Study completion
- Mar 2002
- First posted
- 7 Jul 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and effectiveness of a new drug combination for treating patients with severe aplastic anemia. Patients with aplastic anemia produce too few blood cells, causing fatigue, easy bruising and bleeding, and susceptibility to infections. In many cases, the very low blood counts result from an autoimmune process-that is, the patient's own immune system suppresses production of blood cells by the bone marrow. Although immune-suppressing drugs, such as cyclosporine, can restore normal cell counts, many patients have disease relapses. These patients require long-term therapy with cyclosporine, which can cause harmful side effects. This study will examine whether a lower dose of cyclosporine given together with mycophenolate mofetil (MMF) can maintain blood counts as effectively as full-dose cyclosporine treatment, and whether MMF alone can reduce the chances of future relapses.
Patients 4 years of age and older with severe aplastic anemia who have relapsed after immune suppressing therapy may be eligible for this study. Participants will be randomly assigned to receive either standard cyclosporine therapy or experimental therapy with cyclosporine and MMF.
Patients receiving standard cyclosporine therapy will receive a full dose of the drug for at least 3 months. Those taking both cyclosporine and MMF will take MMF plus half-dose cyclosporine for 3 months and continue MMF for an additional 6 months. Both drugs are taken twice a day by mouth. All patients will have about 120 milliliters (4 ounces) of blood drawn at the beginning of the study to evaluate immune system activity and bone marrow function, and to look for genetic material of certain viruses. Bone marrow aspirations and biopsies will be done at the beginning of the study, and at 6 and 12 months. For these tests, the area of the hip is anesthetized and a special needle is used to draw bone marrow from the hipbone.
The patient's local doctor will be asked to do blood tests for chemistries, liver function and cyclosporine levels weekly for the first month and then every other week. Patients will return to NIH for evaluations 3, 6 and 12 months after treatment and then once a year. About 100 ml (7 tablespoons) of blood will be drawn at each visit.
Detailed description
Aplastic anemia is characterized by trilineage hematopoietic failure with an apparently empty bone marrow. While the precise mechanism of disease has yet to be elucidated, much evidence indicates an immunologically mediated pathophysiology. Clinical trials have shown that approximately 75-80% of patients who are treated with immunosuppressive drugs, especially the combination of antithymocyte globulin (ATG) and cyclosporine (CSA), demonstrate a return of hematopoieses and improved blood counts. This therapy now is considered standard care for the treatment of aplastic anemia in all patients who lack a histocompatibility antigen-matched sibling donor and also in older patients regardless of donor status. However, with longer length of evaluation of patients after initial treatment, it is becoming increasingly clear that a substantial proportion will suffer relapse of pancytopenia. ATG and CSA do not appear to cure the disease in these patients but only disrupt a chronic autoimmune process. Recent data from our own series of patients treated with ATG and CSA, and studies of European patients who are treated with antilymphocyte globulin (ALG) and CSA, indicate that approximately 1/3 of responding patients will relapse and require treatment within 1-2 years of discontinuation of CSA. About 15% of patients become dependent on continued CSA administration in order to maintain blood counts. Chronic CSA toxicities include increased susceptibility to infections, hypertension, and irreversible renal damage, as well as hypertrichosis, hyperaesthesias, gingival hyperplasia, headaches, tremors, and other troubling complaints; there is also a possible increased risk of late malignant diseases. Therefore, a major priority in clinical research in aplastic anemia is the development of strategies to produce more durable responses, as well as to identify immunosuppressive agents that can be used as effectively and with fewer side affects than cyclosporine. Mycophenolate mofetil (MMF) is a novel immunosuppressive drug with proven efficacy in the treatment of graft rejection in renal transplantation. MMF has a different toxicity profile from cyclosporine, and specifically does not damage the kidneys. In this study, we will randomize patients who are judged to have relapsed to receive either standard treatment with full dose cyclosporine or half dose cyclosporine combined with MMF. We anticipate that the combination of cyclosporine with MMF will be as effective as conventional high dose cyclosporine for the purpose of treating relapse of aplastic anemia and would provide a less toxic regimen for long-term treatment of this disease.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate mofetil | Drug | – |
| Cyclosporine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7780125Young NS, Barrett AJ. The treatment of severe acquired aplastic anemia. Blood. 1995 Jun 15;85(12):3367-77. No abstract available.
- Background: PubMed 9005753Young NS. Autoimmunity and its treatment in aplastic anemia. Ann Intern Med. 1997 Jan 15;126(2):166-8. doi: 10.7326/0003-4819-126-2-199701150-00014. No abstract available.
- Background: PubMed 7756640Rosenfeld SJ, Kimball J, Vining D, Young NS. Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood. 1995 Jun 1;85(11):3058-65.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate mofetil and Cyclosporine in people with Aplastic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005935, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.