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

  • End date
    Jan 12, 2025
  • participants needed
  • sponsor
    Children's Hospital of Philadelphia
Updated on 12 March 2022
stem cell transplantation
total body irradiation
flow cytometry
granulocyte colony stimulating factor
transplant conditioning
colony stimulating factor
neutrophil count
severe aplastic anemia
bone marrow failure
shwachman-diamond syndrome
lactate dehydrogenase
paroxysmal nocturnal hemoglobinuria


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.


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.

Condition Acquired Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria, Inherited Bone Marrow Failure Syndromes
Treatment CliniMACs
Clinical Study IdentifierNCT03047746
SponsorChildren's Hospital of Philadelphia
Last Modified on12 March 2022


Yes No Not Sure

Inclusion Criteria

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
i. 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)
ii. 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
platelets < 30,000/µL or transfusion dependence
absolute reticulocyte count < 40,000/µL
iii. Negative evaluation for inherited bone marrow failure conditions (see
iv. Must not have accompanying diagnosis of myelodysplastic syndrome
Patients whose best available donor is a ≤7/10 related donor allele level
HLA match will only be eligible if they have failed prior immune suppressive
therapy. All others may receive study therapy as the initial treatment
Patients who have received prior immune suppression therapy will be eligible
if they have refractory or relapsed disease, defined by persistent
transfusion dependence and/or ANC < 500/µL at least 12 weeks after
initiation of immune suppression therapy
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
i. Elevated Lactate dehydrogenase (LDH)
ii. Low to absent serum haptoglobin
iii. Hemoglobinuria
iv. Reticulocytosis
v. 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
Fanconi Anemia
To be eligible, patients must meet the following criteria
i. Must have evidence of BM failure, defined as a bone marrow biopsy
demonstrating cellularity of <25% in addition to peripheral blood cytopenias
ii. Must have chromosomal breakage (stress) testing performed demonstrating
increased sensitivity to DNA damage caused by mitomycin C (MMC) or
diepoxybutane (DEB)
iii. 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
i. Must have evidence of BM failure, defined as a bone marrow biopsy
demonstrating cellularity of <25% in addition to peripheral blood cytopenias
ii. Must have lymphocyte telomere length analysis performed at a Clinical
Laboratory Improvement Amendments (CLIA)-certified facility, demonstrating
telomeres <1%ile for age
iii. 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
i. 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
ii. Must have developed trilineage BM failure, including BM cellularity <
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
Severe Congenital Neutropenia
To be eligible, patients must meet the following criteria
i. Have a baseline ANC < 500/µL prior to G-CSF therapy
ii. Require chronic G-CSF therapy greater than 3 doses per week in order to maintain an ANC
> 1000/µL
iii. 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
iv. 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
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
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
Organ function status
Renal: Serum creatinine <1.5x upper limit of normal for age
Hepatic: Transaminases <= 5x upper limit of normal. Bilirubin <2.0 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

Exclusion Criteria

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
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
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 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
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note