Severe Aplastic Anemia Clinical Trial
Official title:
The Natural History of Acquired and Inherited Bone Marrow Failure Syndromes.
Background: Bone marrow failure diseases are rare. Much is known about the diseases at the time of diagnosis, but long-term data about the effects of the diseases and treatments are lacking. Researchers want to better understand long-term outcomes in people with these diseases. Objective: To follow people diagnosed with acquired or inherited bone marrow failure disease and study the long-term effects of the disease and its treatments on organ function. Eligibility: People aged 2 years and older who have been diagnosed with acquired or inherited bone marrow failure or Telomere Biology Disorder. First degree family members may also be able to take part in the study. Design: Participants will be screened with a medical history, physical exam, and blood tests. They may have a bone marrow biopsy and aspiration. For this, a large needle will be inserted in the hip through a small cut. Marrow will be drawn from the bone. A small piece of bone may be removed. Participants may also be screened with some of the following: Cheek swab or hair follicle sample Skin biopsy Urine or saliva sample Evaluation by disease specialists (e.g., lung, liver, heart) Imaging scan of the chest Liver ultrasounds Six-Minute Walk Test Lung function test Participants will be put into groups based on their disease. They will have visits every 1 to 3 years. At visits, they may repeat some screening tests. They may fill out yearly surveys about their medicines, transfusions, pregnancy, bleeding, and so on. They may have other specialized procedures, such as imaging scans and ultrasounds. Participation will last for up to 20 years.
Status | Recruiting |
Enrollment | 1000 |
Est. completion date | February 4, 2041 |
Est. primary completion date | February 4, 2041 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years and older |
Eligibility | - INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all of the following criteria. Subjects and their family members who undergo screening but ultimately do not meet criteria for cohorts 1-5 will be removed from the study. Subjects may forgo screening and sign directly onto cohorts 1-5 if they meet criteria based on either prior NIH testing or external examinations. Family members will only be asked to be screened for participation onto this study after confirmation of eligibility by an affected participant. Cohorts 1-4 - Age >=2 years - Diagnosis of acquired or inherited bone marrow failure or ineffective hematopoiesis or TBD (see below for cohort 3 specific criteria) - Ability and willingness to come to the NIH CC for consultation and testing - Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and their willingness to sign a written informed consent document. - For cohort 3 - TBD: Presence of a pathogenic, likely pathogenic, or known family mutation in a telomere maintenance gene OR If mutation negative or VUS, telomere length <10^th percentile in lymphocytes with at least two clinical features: 1) cytopenia (Hb <10g/dL or ANC <1.5x10^9 or platelets<100), 2) documented liver fibrosis by histology OR abnormal liver US / fibro scan consistent with fatty liver or fibrosis), 3) documented pulmonary fibrosis by histology / Cohort 5 - Age >= 2 years - First degree family member with a known or suspected inherited bone marrow failure syndrome from a patient enrolled on this or another NIH protocol as determined by a PI or AI - Ability and willingness to safely provide blood, buccal swab, or fibroblasts for testing as stated by subject - Ability of subject or Legally Authorized Representative (LAR) to understand the investigational nature of the protocol and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: - Post HSCT (except if cohort 3 - TBD) - MDS/AML on chemotherapy (patients with hypoplastic MDS who have received or are on erythropoietin stimulating agent (ESA), granulocyte colony-stimulating factor (GCSF), or immunosuppressive treatment will not be excluded). Subjects in Cohort 3 with TBD can be seen if they have received chemotherapy for MDS/AML. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Cohort 4: Rate of progression to transfusion dependent marrow failure, marrow failure requiring therapeutic intervention (such as medical therapy or HSCT) or the progression to hematological malignancy | Rate of progression to transfusion dependent marrow failure, marrow failure requiring therapeutic intervention (such as medical therapy or HSCT) or the progression to hematological malignancy. | 20 years | |
Primary | Cohort 3: Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to m... | Development of cytopenias, lung disease or liver disease, or (if present at baseline) characterization, and rate of progression of cytopenias, lung disease or liver disease in TBD patients and looking at their overall contribution to morbidity and mortality. | 20 years | |
Primary | Cohort 1: Rate of relapse and clonal evolution in previously treated patients | Rate of relapse and clonal evolution in previously treated patients | 20 years | |
Primary | Cohort 2: Rate of progression requiring therapeutic intervention | Rate of progression (cytopenias or clonal evolution) requiring therapeutic intervention. | 20 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT02828592 -
Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
|
Phase 2 | |
Completed |
NCT02833805 -
NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
|
Phase 2 | |
Terminated |
NCT01319851 -
Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
|
N/A | |
Completed |
NCT00004143 -
Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
|
Phase 2 | |
Recruiting |
NCT03836690 -
Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
|
Phase 1 | |
Recruiting |
NCT06039436 -
Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT
|
||
Enrolling by invitation |
NCT05049668 -
RACE 2: a Long Term Follow-up of Patients Participating in the RACE Trial
|
||
Recruiting |
NCT01351545 -
A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)
|
||
Recruiting |
NCT01472055 -
Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation
|
Phase 2 | |
Completed |
NCT01703169 -
Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
|
Phase 2 | |
Withdrawn |
NCT01129323 -
Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
|
N/A | |
Completed |
NCT00516152 -
Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT
|
Phase 2 | |
Recruiting |
NCT06069180 -
The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA
|
Phase 4 | |
Recruiting |
NCT03579875 -
Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
|
Phase 2 | |
Recruiting |
NCT05720234 -
Avatrombopag Combined With IST as First-line Treatment for SAA
|
Phase 2 | |
Recruiting |
NCT04304820 -
Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)
|
Phase 2 | |
Terminated |
NCT00358657 -
Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders
|
Phase 2 | |
Completed |
NCT02998645 -
Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia
|
Phase 2 | |
Active, not recruiting |
NCT03825744 -
Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia
|
Phase 3 | |
Not yet recruiting |
NCT06279494 -
Sirolimus+Abatacept+Mycophenolate Mofetil for Prophylaxis of aGVHD in Patients Receiving Haplo-HSCT Who Are Intolerant to Calcineurin Inhibitors
|
Phase 1/Phase 2 |