Severe Aplastic Anemia (SAA)Phase 2NCT00001626
Comparing Therapies for the Treatment of Severe Aplastic Anemia
A Phase 2 study testing antithymocyte globulin, cyclophosphamide and cyclosporine in people with Severe Aplastic Anemia (SAA), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 110 years
- Conditions the study is for
- Severe Aplastic Anemia (SAA)
- What is being tested?
- antithymocyte globulin, cyclophosphamide and cyclosporine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 1997to 3 Mar 2008
- 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 15 to 110 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: 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.
Read more
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.
Read the detailed description
Severe aplastic anemia (SAA) is a disorder with a poor prognosis if untreated. Current accepted therapeutic strategies include bone marrow transplantation (BMT) and immunosuppression, both offering cure or amelioration in the majority of patients. Although BMT is successful using human leukocyte antigen (HLA) matched sibling bone marrow, the 25% probability of finding an HLA identical sibling within a family renders this approach available to only a minority of patients. BMT utilizing HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common, occurring in about a third of responders. Late evolution of aplastic anemia to other serious hematologic disorders is a significant problem following successful treatment with ATG/CSA with paroxysmal nocturnal hemoglobinuria (PNH) occurs in approximately 13%, myelodysplasia in about 10%, and acute leukemia in about 7%. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in 10 patients. In this small group, the overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not seen during a median follow-up of greater than 10 years. In the larger randomized trial proposed here, we will compare sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high dose cyclophosphamide and CSA. Secondary endpoints include response duration, event free survival, and overall survival.
- Conditions
- Severe Aplastic Anemia (SAA)
- Being tested
- antithymocyte globulin, cyclophosphamide, cyclosporine
- Keywords
- Severe Aplastic Anemia, Immunosuppression
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
antithymocyte globulinDrug
antithymocyte globulin
cyclophosphamideDrug
cyclophosphamide
cyclosporineDrug
cyclosporine
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | D1-4 cyclophosphamide 50 mg/kg IV, then cyclosporine starting on d14 at 12 mg/kg/d for 6 months Receives: 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 Receives: Drug: antithymocyte globulin; Drug: cyclosporine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compare the sustained response proportions among patients with SAA treated with immunosuppressive therapy with either ATG/CSA or high dose cyclophosphamide and CSA.
Measured: 12 weeks.
Secondary outcomes (2)
Overall and event-free survival.
Measured: 12 months
Response duration. Evolution to PNH, myelodysplasia, and active leukemia.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start2 Jun 1997
- Primary completion20 Feb 2001
- Study completion3 Mar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Aplastic Anemia (SAA)Studies 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Neal S Young, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001626
- Sponsor's protocol ID
- 970117
- Other IDs
- 97-H-0117
- Status last verified
- Sep 2020
- First submitted
- 3 Nov 1999
- Last updated
- 22 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Antithymocyte Globulin and Cyclosporine Versus Cyclophosphamide and Cyclosporine in the Treatment of Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT00001626
- Acronym / sponsor ID
- 970117
- Conditions
- Severe Aplastic Anemia (SAA)
- Keywords
- Severe Aplastic Anemia, Immunosuppression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 2 Jun 1997 (actual)
- Primary completion
- 20 Feb 2001 (actual)
- Study completion
- 3 Mar 2008 (actual)
- First posted
- 4 Nov 1999 (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.
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.
Detailed description
Severe aplastic anemia (SAA) is a disorder with a poor prognosis if untreated. Current accepted therapeutic strategies include bone marrow transplantation (BMT) and immunosuppression, both offering cure or amelioration in the majority of patients. Although BMT is successful using human leukocyte antigen (HLA) matched sibling bone marrow, the 25% probability of finding an HLA identical sibling within a family renders this approach available to only a minority of patients. BMT utilizing HLA-matched, unrelated donors carries a high risk of treatment failure along with considerable toxicity. While combined immunosuppression with both antithymocyte globulin (ATG) and cyclosporine A (CSA) produces hematologic improvement in most patients, relapse is common, occurring in about a third of responders. Late evolution of aplastic anemia to other serious hematologic disorders is a significant problem following successful treatment with ATG/CSA with paroxysmal nocturnal hemoglobinuria (PNH) occurs in approximately 13%, myelodysplasia in about 10%, and acute leukemia in about 7%. Recently, results of immunosuppression in SAA with another potent immunosuppressive agent, cyclophosphamide, were reported in 10 patients. In this small group, the overall response rate was similar to that seen with ATG/CSA, but relapse and late clonal disease were not seen during a median follow-up of greater than 10 years. In the larger randomized trial proposed here, we will compare sustained hematologic response rates to either conventional immunosuppression with ATG/CSA or high dose cyclophosphamide and CSA. Secondary endpoints include response duration, event free survival, and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: cyclophosphamide, Drug: cyclosporineD1-4 cyclophosphamide 50 mg/kg IV, then cyclosporine starting on d14 at 12 mg/kg/d for 6 months |
| B | Experimental | Drug: antithymocyte globulin, Drug: cyclosporineATG at 40 mg/kg/d for 4 days then cyclosporine at 12 mg /kg/d for 6 months |
Who may qualify
- Ages
- 15 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (10 listed)
- 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.
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 |
|---|---|---|
| antithymocyte globulinantithymocyte globulin | Drug | B |
| cyclophosphamidecyclophosphamide | Drug | A |
| cyclosporinecyclosporine | Drug | A, B |
Primary outcome
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.
2 secondary outcomes
Overall and event-free survival.
Time frame: 12 months
Response duration. Evolution to PNH, myelodysplasia, and active leukemia.
Time frame: 12 months
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 22 Sep 2020.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Neal S Young, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 antithymocyte globulin, cyclophosphamide and cyclosporine in people with Severe Aplastic Anemia (SAA), 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.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2020. 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.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Sep 2020.