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Acquired Aplastic AnemiaNCT03047746

Unrelated And Partially Matched Related Donor PSCT w/ T Cell Receptor (TCR) αβ Depletion for Patients With BMF

A study testing CliniMACs in people with Acquired Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, run by Children's Hospital of Philadelphia at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes. Read more about this study

Who is it for?
Ages Up to 25 years
What is being tested?
CliniMACs
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
1 Feb 2017to May 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

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 Up to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Acquired and Inherited Bone Marrow Failure Conditions Associated with Trilinear Bone Marrow Failure
  • Acquired Aplastic Anemia
  • Must meet criteria for severe or very severe aplastic anemia (AA), defined by:
  • Bone marrow biopsy demonstrating cellularity of <25% overall or bone marrow biopsy that is overall hypocellular for age by pathology report with reductions in any two hematopoietic lineages (myeloid, erythroid, or megakaryocyte)
  • In addition, 2 of the following must be met:
  • absolute neutrophil count (ANC) < 500/µL (severe) or < 200/µL (very severe). Current ANC or last ANC prior to start of Granulocyte-colony stimulating factor (G-CSF) may be used.
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  • platelets < 30,000/µL or transfusion dependence
  • absolute reticulocyte count < 40,000/µL
  • Negative evaluation for inherited bone marrow failure conditions (see below)
  • Must not have accompanying diagnosis of myelodysplastic syndrome
  • Patients meeting other eligibility criteria may receive study therapy as the initial treatment approach provided an eligible unrelated or mismatched related ("haplo") donor is available
  • Patients who have received prior immune suppression therapy will be eligible if they have refractory or relapsed disease defined as per treating clinician's judgement, at least 12 weeks after initiation of immune suppression therapy. Relapsed patients who previously met hematologic criteria for severe aplastic anemia do not have to meet these hematologic criteria for severe aplastic anemia at time of relapse to be eligible for transplant.
  • Paroxysmal Nocturnal Hemoglobinuria
  • Patients must have testing (eg. Flow Cytometry demonstrating cells with absent cluster of differentiation 55 (CD55) or cluster of differentiation 59 (CD59) expression demonstrating a PNH clone in greater than 10% of peripheral blood red blood cells and/or granulocytes, along with clinical or laboratory evidence of intravascular hemolysis, such as:
  • Elevated Lactate dehydrogenase (LDH)
  • Low to absent serum haptoglobin
  • Hemoglobinuria
  • Reticulocytosis
  • Studies demonstrating aberrant complement activation
  • Patients who have small paroxysmal nocturnal hemoglobinuria (PNH) clones, no evidence of hemolysis, and meet criteria for severe or very severe AA as defined above, will be classified as acquired AA for treatment stratification.
  • Fanconi Anemia
  • To be eligible, patients must meet the following criteria:
  • Must have evidence of BM failure, defined as a bone marrow biopsy demonstrating cellularity of <25% in addition to peripheral blood cytopenias
  • Must have chromosomal breakage (stress) testing performed demonstrating increased sensitivity to DNA damage caused by mitomycin C (MMC) or diepoxybutane (DEB)
  • Specific testing to define the subtype of Fanconi Anemia through genetic sequencing for causative mutations or complementation group studies is strongly recommended, though not required.
  • Dyskeratosis Congenita and related telomere disorders
  • To be eligible, patients must meet the following criteria:
  • Must have evidence of BM failure, defined as a bone marrow biopsy demonstrating cellularity of <25% in addition to peripheral blood cytopenias
  • Must have lymphocyte telomere length analysis performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified facility, demonstrating telomeres <1%ile for age
  • Specific gene sequencing testing to define the causative genetic mutation is strongly recommended, though not required.
  • Shwachman-Diamond Syndrome
  • To be eligible, patients must meet the following criteria:
  • Must have genetic testing confirming a mutation in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, and/or classic clinical features of Shwachman-Diamond Syndrome, including pancreatic insufficiency, musculoskeletal anomalies, and endocrinopathies
  • Must have developed trilineage BM failure, including BM cellularity < 25%.
  • Patients meeting the above criteria for Shwachman-Diamond syndrome will be eligible for conditioning regimen #1 with dosing of Total Body Irradiation (TBI) and cyclophosphamide according to the dyskeratosis congenita regimen
  • Inherited Bone Marrow Failure Conditions Associated with Predominant Single Lineage Failure
  • Severe Congenital Neutropenia
  • 1. To be eligible, patients must meet the following criteria:
  • Have a baseline ANC < 500/µL prior to G-CSF therapy
  • Require chronic G-CSF therapy greater than 3 doses per week in order to maintain an ANC > 1000/µL
  • Have genetic testing demonstrating mutation(s) in a gene known to cause severe congenital neutropenia and/or have negative testing for autoimmune causes of neutropenia or BM biopsy demonstrating myeloid lineage arrest at neutrophil precursor stage.
  • History of severe bacterial or fungal infection associated with neutropenia, including, but not limited to, pneumonia, osteomyelitis, mastoiditis, or bacteremia. If no infection history, must otherwise have evidence of toxicity due to chronic G-CSF therapy, including osteopenia, splenomegaly or isolated cytogenetic abnormalities.
  • Isolated disorders of erythropoiesis:
  • 1. Includes, but not limited to: i. Diamond-Blackfan Anemia (DBA) ii. Congenital Dyserythropoietic Anemia (CDA) iii. Congenital Sideroblastic Anemia (CSA) 2. Eligibility criteria include: i. Chronic red blood cell (RBC) Transfusion Dependence, with minimum frequency of every 8 weeks ii. BM aspirate and biopsy demonstrating selective erythroid hypoplasia or dyserythropoiesis iii. For patients with DBA, must have failed at least one therapeutic trial with corticosteroids iv. Acquired viral and autoimmune causes of hypo-productive anemia have been excluded v. Specific genetic testing attempting to define the causative mutation is recommended but not required
  • o Congenital Thrombocytopenia Syndromes
  • 1. Includes, but is not limited to, patients with Congenital Amegakaryocytic Thrombocytopenia caused by mutations in the MPL gene 2. Eligibility criteria include: i. Platelet transfusion dependence with a minimum transfusion frequency of every 8 weeks ii. Infectious, autoimmune, and other causes of secondary thrombocytopenia have been excluded iii. Genetic sequencing of the MPL gene is required iv. Additional genetic testing for causes of familial thrombocytopenia is recommended but not required
  • Organ function status
  • Renal: Serum creatinine <1.5x upper limit of normal for age
  • Hepatic: Transaminases <500 upper limit of normal. Bilirubin <2.5 mg/dL, (unless elevation due to Gilberts disease or known hemolytic anemia).
  • Cardiac: shortening fraction >= 27%
  • Pulmonary: Diffusing Capacity (DLCO) >= 50% predicted in patients old enough to comply with pulmonary function testing (PFTs) or no baseline oxygen requirement for younger patients.
  • Lansky or Karnofsky performance >= 60
  • Infectious disease criteria
  • No active, untreated infections
  • Patients with likely bacterial infections must be receiving appropriate antibacterial therapy and demonstrating therapy response
  • Patients with likely fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
  • Patients with symptoms consistent with active viral infection will be deferred until viral symptoms resolve. Patients with evidence of cytomegalovirus (CMV), Epstein-Barr virus (EBV) or other known viremia must receive appropriate therapy to clear viremia prior to initiating study therapy.
  • Signed consent by parent/guardian or able to give consent if >= 18 years

Who cannot join

  • Patients who do not meet disease, organ or infectious criteria.
  • Patients with a clinical diagnosis of myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
  • Patients with no suitable closely Human leukocyte antigen (HLA)-matched unrelated or related haploidentical matched donor available. Patients with suitable fully matched related donor are also not eligible.
  • Pregnant females. All females of childbearing potential must have negative pregnancy test.
  • Donor selection and eligibility:
  • Donor selection will comply with 21 Code of Federal Regulations (CFR 1271) of the U.S. Food and Drug Administration's Code of Federal Regulations
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  • Donor testing:
  • Unrelated donor meets National Marrow Donor Program criteria for donation
  • For partially matched related donors, Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) standard procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. The donor collection program is FACT accredited.
  • For partially matched related donors, if subject has genetically confirmed iBMF syndrome, related donor must be evaluated for this disorder and testing must be negative
  • Infectious disease testing of donor will be per current Blood and Marrow Transplant Program Standards of Practice as per 21 CFR Part 1271. Donor medical records and history are reviewed to confirm that the donor is free of infectious risk factors and meets donor eligibility criteria as defined by 21 CFR 127.
  • Donor matching
  • High resolution HLA typing at HLA-A, -B, -C, DRB1, and DQB1 loci
  • Unrelated donor
  • Donor must be an antigen and allele match at ≥ 8/10 HLA Loci
  • In donor with 2 mismatches, only one mismatch involving HLA-A, -B, or -DRB1 will be allowed
  • Donor and collection center willing to undergo mobilization and apheresis
  • Partially matched related donor
  • Related donor must be ≥ 5/10 but < 10/10 HLA match
  • Donor must be willing to undergo G-CSF mobilization and stem cell apheresis.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Unrelated And Partially Matched Related Donor Peripheral Blood Stem Cell Transplantation (PSCT) With TCR αβ + T Cell And B Cell Depletion For Patients With Acquired And Inherited Bone Marrow Failure

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.

Read the detailed description

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes. Previously established, disease-specific transplant preparative regimens will be administered based on the specific underlying BMF condition. Mobilized PBSC will be processed using the CliniMACS system for TCR alpha/beta+ T cell depletion plus cluster of differentiation 19+ (CD19+) B cell depletion. The study will determine efficacy of this strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and one year overall and event-free survival.

Being tested
CliniMACs
Medical subject headings
Hemoglobinuria, Paroxysmal, Congenital Bone Marrow Failure Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CliniMACsDevice

    Peripheral blood stem cells from closely matched unrelated or partially matched related donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique

Study groups in NCT03047746
Study groupRoleWhat they receive
TCRalpha/beta Tcell Depletion for BMF with trilineage aplasiaOtherPatients with acquired or inherited bone marrow failure (iBMF) with trilineage aplasia excluding Fanconi Anemia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.
Receives: Device: CliniMACs
TCRalpha/beta Tcell Depletion for BMF w/o trilineage aplasiaOtherPatients with acquired or inherited bone marrow failure (iBMF) without trilineage aplasia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.
Receives: Device: CliniMACs
TCRalpha/beta Tcell Depletion for BMF w/ Fanconi AnemiaOtherPatients with acquired or inherited bone marrow failure (iBMF) with Fanconi Anemia and related DNA Repair Disorders will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.
Receives: Device: CliniMACs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of graft failure

    Measured: Up to three years post-transplantation

  2. Time to neutrophil engraftment

    Measured: Up to 60 days post-transplantation

  3. Incidence of acute graft vs. host disease (GVHD)

    Measured: Up to 100 days post-transplantation

  4. Incidence of chronic graft vs. host disease (GVHD)

    Measured: Up to three years post-transplantation

Secondary outcomes (4)

  1. Treatment-related Mortality (TRM)

    Measured: Up to 100 days post-transplantation

  2. Probability of event-free survival (EFS)

    Measured: Up to 1 year post-transplantation

  3. Probability of overall survival (OS)

    Measured: Up to 1 year post-transplantation

  4. Reactivation/Infection from CMV, EBV, adenovirus

    Measured: Up to 1 year post-transplantation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2017 (estimated)
  2. Study start1 Feb 2017
  3. Primary completionMay 2028 (estimated)
  4. Study completionMay 2029 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03047746
Sponsor's protocol ID
16-012881
Status last verified
Jun 2026
First submitted
7 Feb 2017
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing CliniMACs in people with Acquired Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, run by Children's Hospital of Philadelphia 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 58 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2026. 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Rate of graft failure (time frame: Up to three years post-transplantation). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03047746.

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 17 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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