NCT03520647 · National Heart, Lung, and Blood Institute (NHLBI)
Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis
What this study is about
Background: Severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too.
View original scientific description
Background: Severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) cause serious blood problems. Stem cell transplants using bone marrow or blood plus chemotherapy can help. Researchers want to see if using peripheral blood stem cells (PBSCs) rather than bone marrow cells works too. PBSCs are easier to collect and have more cells that help transplants. Objectives: To see how safely and effectively SAA, MDS and PNH are treated using peripheral blood hematopoietic stem cells from a family member plus chemotherapy. Eligibility: Recipients ages 4-60 with SAA, MDS or PNH and their relative donors ages 4-75 Design: Recipients will have: * Blood, urine, heart, and lung tests * Scans * Bone marrow sample Recipients will need a caregiver for several months. They may make fertility plans and a power of attorney. Donors will have blood and tissue tests, then injections to boost stem cells for 5-7 days. Donors will have blood collected from a tube in an arm or leg vein. A machine will separate stem cells and maybe white blood cells. The rest of the blood will be returned into the other arm or leg. In the hospital for about 1 month, recipients will have: * Central line inserted in the neck or chest * Medicines for side effects * Chemotherapy over 8 days and radiation 1 time * Stem cell transplant over 4 hours Up to 6 months after transplant, recipients will stay near NIH for weekly physical exams and blood tests. At day 180, recipients will go home. They will have tests at their doctor s office and NIH several times over 5 years.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- - RECIPIENT:
- Diagnosed with severe aplastic anemia with bone marrow cellularity \<30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count less than or equal to 1000 cells/ microL or for patients receiving granulocyte transfusions, absolute neutrophil count less than or equal to 1000 cells/microL before beginning granulocyte transfusions). OR --History of severe aplastic anemia transformed to MDS. that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) \<5% myeloblasts and \<30% of cellularity in the bone marrow on screening morphologic analysis. OR
- PNH that is either refractory to treatment with eculizumab/ravulizumab or occurs in patients who don t have access to treatment with eculizumab associated with either a) life- threatening thrombosis and/or b) cytopenia associated with transfusion dependence and/or c) recurrent and debilitating hemolytic crisis.
- Subjects with severe aplastic anemia, hypoplastic MDS or PNH with associated bone marrow failure syndromes who have intolerance of or failure to respond to immunosuppressive therapy. This also includes patients who have failed immunosuppressive therapy with ATG and cyclosporine or therapy with cyclosporine combined with eltrombopag in those who are intolerant of or do not have access to treatment with ATG.
- Availability of at least one HLA- haploidentical related donor (i.e. \>= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) to serve as a stem cell donor for the allogeneic transplant.
- Availability of a backup stem cell source in the event of graft rejection:
- at least one additional haploidentical related alternative donor (i.e. HLA- haploidentical related donor (i.e. \>= 5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or \>= 9/10 HLA matched unrelated donor who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the haplo-transplant has been rejected.
- umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the haplo-transplant has been rejected
- The patient does not have any HLA antibodies detectable against any of the mismatched HLA alleles expressed by the haplo-donor.
- Ages 4-60 years inclusive.
- Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.
Exclusion criteria
- - RECIPIENT (ANY OF THE FOLLOWING):
- Availability of an HLA identical (12/12) matched related or unrelated donor who is available within optimal timeline and suitable considering graft source and established donor selection factors (e.g. age, sex, viral exposure, ABO compatibility, pregnancy status, etc) per PI discretion.
- The patient is deemed to be a candidate for a 12/12 HLA matched unrelated stem cell transplant (availability of a donor and resources required for such a transplant).
- ECOG performance status of 2 or more.
- Major anticipated illness or organ failure incompatible with survival from transplant.
- Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year.
- HIV positive.
- Diagnosis of Fanconi s anemia (by chromosome breakage study).
- Diffusion capacity of carbon monoxide (DLCO) \<40% using DLCO corrected for Hgb or lung volumes (patients under the age of 10 may be excluded from this criterion if they have difficulty performing the test correctly and thus are unable to have their DLCO assessed).
- Left ventricular ejection fraction \<40% (evaluated by ECHO)
- Transaminases \> 5x upper limit of normal.
- Direct bilirubin \>3 mg/dl.
- Creatinine clearance \< 50 cc/min/BSAm\^2 by 24-hour urine collection adjusted by body surface area.
- Serum creatinine \> 2.5 mg/dl
- Presence of an active infection not adequately responding to appropriate therapy.
- History of a malignant disease liable to relapse or progress within 5 years. INCLUSION CRITERIA - DONOR: Donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study. EXCLUSION CRITERIA - RELATED DONOR: None
Where
- Bethesda, Maryland
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jul 2, 2026 · Source of record for eligibility and locations