Aplastic AnemiaPhase 1NCT00011830
Stem Cell Mobilization Potential in Patients With Aplastic Anemia in Remission
A Phase 1 study testing G-CSF and Apheresis 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 1) whether it is possible to collect enough stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) from patients with aplastic anemia to use for future treatment, and 2) whether patients who have been treated successfully and relapse will benefit… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- G-CSF and Apheresis
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2001to Feb 2006
- Phase
- Phase 1
- 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
Who may be able to join
- History of severe AA as defined by a hypocellular bone marrow and depression of two out of three peripheral counts as indicated below:
- ANC less than 0.5 x 10 (9)/L;
- platelet count less than 20 x10 (9)/L,
- reticulocyte count less than 60 x 10 (9)/L.
- Demonstrated hematologic response to first or second course of immunosuppression or growth factors or exhibit a spontaneous remission as defined by all peripheral counts as indicated below (must be at least 3 months following the initial course of immunosupressive or growth factor therapy and must be sustained for at least 3 week)
- ANC greater than 1.5 x 10 (9)/L
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- platelet count greater than 80 x10 (9)/L
- hemoglobin greater than 10 g/dl (not transfused)
- Weight > 18 kg
- Age greater than or equal to 2 years
- Able to comprehend the investigational nature of the protocol and be willing to sign an informed consent/assent.
Who cannot join
- Current diagnosis or past history of myelodysplastic syndrome, Fanconis anemia, dyskeratosis congenita or other congenital forms of aplastic anemia.
- Evidence of uncontrolled infection
- ECOG performance status of 2 or more
- Inadequate organ function as defined:
- bilirubin greater than 4.0 mg/dl and
- transaminases greater than than 2 x ULN.
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- Current therapy for malignancy
- HIV infection
- Unfit to receive G-CSF and undergo apheresis (uncontrolled hypertension, currently active ischemic heart disease, unstable arrhythmia, history of chest pain, myocardial infarction, peripheral vascular disease, transient ischemic attack, or stroke).
- Psychiatric, affective or any other disorder that would compromise ability to give informed consent
- Moribund or patients with concurrent hepatic, renal, cardiac, metabolic disease of such severity that death within 1-4 weeks from the initiation of the therapy is likely.
- An enlarged spleen by physical exam.
- Pregnant or lactating.
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 Pilot Study of G-CSF Induced Stem Cell Mobilization Potential in Patients With Relapsed Severe Aplastic Anemia
This study will examine 1) whether it is possible to collect enough stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) from patients with aplastic anemia to use for future treatment, and 2) whether patients who have been treated successfully and relapse will benefit from autologous stem cell transfusion (transfusion of their own stem cells).
Patients 12 years of age or older with aplastic anemia who have been successfully treated with immunosuppressive drugs and are now in remission may be eligible for this study. Participants will undergo a complete history and physical examination, bone marrow biopsy (removal of a small sample of bone marrow from the hip bone) and blood tests, plus procedures to collect stem cells, as follows:
- G-CSF (Filgrastim) administration - G-CSF will be given by injection under the skin daily for up to 10 days. This drug causes stem cells to move from the marrow into the blood where they can be collected more easily.
- Apheresis - Stem cells will be collected through apheresis, usually starting the 5th to 6th day of Filgrastim injections. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a cell separator machine where the white cells and stem cells are removed. The red cells, platelets and plasma are returned to the body through a second needle in the other arm. The procedure takes about 5 hours. Up to five procedures, done on consecutive days, may be required to collect enough cells for transplantation. If enough cells are collected, they will be purified (treated to remove the white blood cells) using an experimental device. Removing the lymphocytes may reduce the chance of relapse of aplastic anemia following the stem cell transplant. The stem cells will be frozen for later use, if needed.
- Follow-up - Participants are followed at NIH at 6-month intervals.
Read the detailed description
Immune mechanisms are responsible for hematopoietic failure in most cases of acquired aplastic anemia (AA), a disease characterized by hypocellular bone marrow and pancytopenia. In aplastic anemia, much experimental data points toward an immune-mediated pathophysiology of destruction of hematopoietic progenitor and stem cells. Clinically, immunosuppressive therapies, usually anti-thymocyte globulin (ATG) and cyclosporine (CsA), have been shown to be effective in a large proportion of patients with severe AA. However, at 2 years after initial treatment as many as 35% of patients with initially good response and normal blood counts relapse and require repeated cycles of intense immunosuppression and/or chronic immunosuppressive regimens. Although relapse in previously immunosuppression-responsive patients has a generally good prognosis, there is an increased risk of complications and treatment-related toxicities. The outlook of patients who fail to respond to repeated intensive immunosuppression is poor. While it is likely that some of the treatment failures occurring with conventional immunosuppressive regimens (both at presentation and in relapsed patients) may be due to inability to suppress the autoimmune process leading to the bone marrow failure, more intense therapies such as cyclophosphamide have a high complication rate due to prolonged and dose-related myelosuppression. In this protocol, we propose that patients with severe AA who show a good response to the initial round of immunosuppression undergo stem cell mobilization, collection, and cryopreservation.
This pilot study of 20 patients is designed to evaluate: 1) the CD34+ cell mobilization response to administration of standard doses of granulocyte-colony stimulating factor (G-CSF) and 2) the potential for collecting stem cells from patients with a history of severe AA who have been given G-CSF. Outcome parameters to be monitored are the mobilization response to G-CSF, and the safety profile and tolerance of G-CSF and leukapheresis. Effectiveness will be gauged by historical comparison of these parameters to normal healthy age-matched volunteers.
It is important to point out that there is no therapeutic intent to the majority of this protocol or direct benefit for enrolled patients. We do plan, however, to cryopreserve the remainder of the mobilized cells collected by apheresis for possible autologous transplantation in the event of the patient's progression to leukemia or bone marrow failure in the future.
- Conditions
- Aplastic Anemia
- Being tested
- G-CSF, Apheresis
- Keywords
- Stem Cell Cryopreservation, Leukapheresis
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFDrug
ApheresisProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2001 (estimated)
- Study startFeb 2001
- Study completionFeb 2006
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 1
- Primary purpose
- Treatment
- Enrolment
- 20 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00011830
- Sponsor's protocol ID
- 010083
- Other IDs
- 01-H-0083
- Status last verified
- Feb 2006
- First submitted
- 28 Feb 2001
- 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 7780125Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.
PubMed 2981406Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.
PubMed 9134878
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 Pilot Study of G-CSF Induced Stem Cell Mobilization Potential in Patients With Relapsed Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT00011830
- Acronym / sponsor ID
- 010083
- Conditions
- Aplastic Anemia
- Keywords
- Stem Cell Cryopreservation, Leukapheresis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Feb 2001
- Study completion
- Feb 2006
- First posted
- 1 Mar 2001 (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 1) whether it is possible to collect enough stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) from patients with aplastic anemia to use for future treatment, and 2) whether patients who have been treated successfully and relapse will benefit from autologous stem cell transfusion (transfusion of their own stem cells).
Patients 12 years of age or older with aplastic anemia who have been successfully treated with immunosuppressive drugs and are now in remission may be eligible for this study. Participants will undergo a complete history and physical examination, bone marrow biopsy (removal of a small sample of bone marrow from the hip bone) and blood tests, plus procedures to collect stem cells, as follows:
- G-CSF (Filgrastim) administration - G-CSF will be given by injection under the skin daily for up to 10 days. This drug causes stem cells to move from the marrow into the blood where they can be collected more easily.
- Apheresis - Stem cells will be collected through apheresis, usually starting the 5th to 6th day of Filgrastim injections. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a cell separator machine where the white cells and stem cells are removed. The red cells, platelets and plasma are returned to the body through a second needle in the other arm. The procedure takes about 5 hours. Up to five procedures, done on consecutive days, may be required to collect enough cells for transplantation. If enough cells are collected, they will be purified (treated to remove the white blood cells) using an experimental device. Removing the lymphocytes may reduce the chance of relapse of aplastic anemia following the stem cell transplant. The stem cells will be frozen for later use, if needed.
- Follow-up - Participants are followed at NIH at 6-month intervals.
Detailed description
Immune mechanisms are responsible for hematopoietic failure in most cases of acquired aplastic anemia (AA), a disease characterized by hypocellular bone marrow and pancytopenia. In aplastic anemia, much experimental data points toward an immune-mediated pathophysiology of destruction of hematopoietic progenitor and stem cells. Clinically, immunosuppressive therapies, usually anti-thymocyte globulin (ATG) and cyclosporine (CsA), have been shown to be effective in a large proportion of patients with severe AA. However, at 2 years after initial treatment as many as 35% of patients with initially good response and normal blood counts relapse and require repeated cycles of intense immunosuppression and/or chronic immunosuppressive regimens. Although relapse in previously immunosuppression-responsive patients has a generally good prognosis, there is an increased risk of complications and treatment-related toxicities. The outlook of patients who fail to respond to repeated intensive immunosuppression is poor. While it is likely that some of the treatment failures occurring with conventional immunosuppressive regimens (both at presentation and in relapsed patients) may be due to inability to suppress the autoimmune process leading to the bone marrow failure, more intense therapies such as cyclophosphamide have a high complication rate due to prolonged and dose-related myelosuppression. In this protocol, we propose that patients with severe AA who show a good response to the initial round of immunosuppression undergo stem cell mobilization, collection, and cryopreservation.
This pilot study of 20 patients is designed to evaluate: 1) the CD34+ cell mobilization response to administration of standard doses of granulocyte-colony stimulating factor (G-CSF) and 2) the potential for collecting stem cells from patients with a history of severe AA who have been given G-CSF. Outcome parameters to be monitored are the mobilization response to G-CSF, and the safety profile and tolerance of G-CSF and leukapheresis. Effectiveness will be gauged by historical comparison of these parameters to normal healthy age-matched volunteers.
It is important to point out that there is no therapeutic intent to the majority of this protocol or direct benefit for enrolled patients. We do plan, however, to cryopreserve the remainder of the mobilized cells collected by apheresis for possible autologous transplantation in the event of the patient's progression to leukemia or bone marrow failure in the future.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- History of severe AA as defined by a hypocellular bone marrow and depression of two out of three peripheral counts as indicated below:
- ANC less than 0.5 x 10 (9)/L;
- platelet count less than 20 x10 (9)/L,
- reticulocyte count less than 60 x 10 (9)/L.
- Demonstrated hematologic response to first or second course of immunosuppression or growth factors or exhibit a spontaneous remission as defined by all peripheral counts as indicated below (must be at least 3 months following the initial course of immunosupressive or growth factor therapy and must be sustained for at least 3 week)
Key exclusion criteria (13 listed)
- Current diagnosis or past history of myelodysplastic syndrome, Fanconis anemia, dyskeratosis congenita or other congenital forms of aplastic anemia.
- Evidence of uncontrolled infection
- ECOG performance status of 2 or more
- bilirubin greater than 4.0 mg/dl and
- transaminases greater than than 2 x ULN.
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 |
|---|---|---|
| G-CSF | Drug | – |
| Apheresis | Procedure or surgery | – |
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 2981406Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young NS. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257-65. doi: 10.1056/NEJM198501313120501.
- Background: PubMed 9134878Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. doi: 10.1056/NEJM199705083361906. No abstract available.
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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 1 study testing G-CSF and Apheresis 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.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 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 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 NCT00011830, 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.