Stem Cell Mobilization Potential in Patients With Aplastic Anemia in Remission
|ClinicalTrials.gov Identifier: NCT00011830|
Recruitment Status : Completed
First Posted : March 1, 2001
Last Update Posted : March 4, 2008
|First Submitted Date ICMJE||February 28, 2001|
|First Posted Date ICMJE||March 1, 2001|
|Last Update Posted Date||March 4, 2008|
|Study Start Date ICMJE||February 2001|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00011830 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Stem Cell Mobilization Potential in Patients With Aplastic Anemia in Remission|
|Official Title ICMJE||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:
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 Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||Aplastic Anemia|
|Study Arms||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date||February 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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
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.
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.
Current therapy for malignancy
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.
|Ages||Child, Adult, Older Adult|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00011830|
|Other Study ID Numbers ICMJE||010083
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP