Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome

  • End date
    Mar 1, 2028
  • participants needed
  • sponsor
    National Heart, Lung, and Blood Institute (NHLBI)
Updated on 14 June 2022
stem cell transplantation
bone marrow transplant
umbilical cord blood transplantation
blood test
neutrophil count
aplastic anemia



Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective.


To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective.


Recipients ages 4-60 with SAA or MDS

Donors ages 4-75


Recipients will be screened with:

  • Blood, lung, and heart tests
  • Bone marrow biopsy
  • CT scan

Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose.

Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits:

  • First 3-4 months: 1-2 times weekly
  • Then every 6 months for 5 years<TAB>

Donors will be screened with:

  • Physical exam
  • Medical history
  • Blood tests

Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein.

Donors will get filgrastim injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.


Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are life-threatening bone marrow disorders. For SAA patients, long term survival can be achieved with immunosuppressive treatment. However, of those patients treated with immunosuppressive therapy, one quarter to one third will not respond, and about 50% of responders will relapse.

Combined haplo-cord transplant as an alternative to cord or haploidentical donor alone transplantation has recently been shown to be a viable transplant option for SAA patients lacking an HLA matched donor. In our ongoing protocol 08-H-0046, we have utilized this approach in 25 patients with SAA with 23/25 patients having sustained engraftment and long-term disease free/transfusion free survival. However, engraftment patterns have varied substantially and in some patients, cord engraftment was profoundly delayed or never occurred. A number of strategies to expand hematopoietic progenitor cells (HPC) in vitro to improve engraftment and prevent graft rejection have recently been studied. Nicotimanide (NAM) expanded umbilical cord blood/unrelated cord blood (UCB) can be successfully engrafted in NOD/SCID mice (1) and humans (2) where they appear to have long-term repopulating potential. CordIn(TM) is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells. CordIn(TM) comprises: 1) Ex vivo expanded, umbilical cord blood-derived hematopoietic CD34+ progenitor cellsU ( (CordIn(TM) cultured fraction (CF)); and 2) the non-cultured cell fraction of the same CBU (CordIn(TM) Non-cultured Fraction (NF)) consisting of mature myeloid and lymphoid cellsU. Both fractions, i.e. CordIn(TM) CF and CordIn(TM) NF are kept frozen until they are infused on the day of transplantation.

This research protocol is therefore designed to evaluate the safety and effectiveness of transplantation with ex vivo expanded UCB (CordIn(TM)) to overcome the high incidence of graft rejection associated with conventional UCB for aplastic anemia, where graft rejection occurs in up to 50% of subjects. We believe, based on preliminary data, that transplantation of CordIn(TM) will not only lead to rapid engraftment, but will also lead to sustained hematopoiesis, expedited immune recovery, and will reduce the chance of cord graft failure in this setting, potentially obviating the need for co-transplanting haploidentical CD34+ cells as a stem cell back-up. This phase II study is designed to have two cohorts: cohort 1 is intended to establish (in as safe a manner as possible) preliminary pilot data to support the capacity for the CordIn unit to engraft in patients with SAA in the presence of haplo CD34+ cells. For cohort 1, three to six subjects will be conditioned then will be transplanted with the thawed CordIn(TM) unit (consisting of the cultured fraction and the non-cultured fraction of the same CBU) and approximately 3 x 106 CD34+ cells/kg from a haploidentical donor which will serve as a backup stem cell source should cord graft failure occur. If 3 of the first 3 to 4 subjects or 4 of 6 subjects achieve early and sustained engraftment (defined as ANC >500 cells/ul by day 26 and a calculated cord ANC >500 cells /ul by day 42 sustained at day 100), the study will move to cohort 2 where up to 23 subsequent subjects will be transplanted with the CordIn(TM) unit alone.

The primary objective of the Phase II study is to evaluate the ability of the CordIn(TM) unit to achieve sustained early engraftment. Secondary endpoints will include 100 day and 200 day treatment related mortality (TRM), and standard transplant outcome variables such as non-hematologic toxicity, incidence and severity of acute and chronic GVHD, and relapse of disease. Health related quality of life will also be assessed as secondary outcome measure.

Condition Severe Aplastic Anemia, Hypo-Plastic MDS, Myelodysplastic Syndrome (MDS)
Treatment CordIn, CordIn(TM), Omidubicel (formerly Nicord (Registered Trademark) and Cordin (TM))
Clinical Study IdentifierNCT03173937
SponsorNational Heart, Lung, and Blood Institute (NHLBI)
Last Modified on14 June 2022


Yes No Not Sure

Inclusion Criteria

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 <=1000 cells/ uL or for patients receiving granulocyte transfusions, absolute neutrophil count <=1000 cells/ uL before beginning granulocyte transfusions)
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
Identification of either a) at least one alternative donor (i.e. HLA- haploidentical
Intolerance of or failure to respond to standard immunosuppressive therapy
related donor (i.e. greater than or equal to 5/10 HLA match: HLA-A, B, C, DR, and DQ
loci) or greater than or equal to 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
Ages 4-60 years inclusive
the CordIn unit has been rejected or b) umbilical cord blood unit/s that can be used
for a salvage cord blood transplant in the event that the CordIn unit has been
Availability of at least one greater than or equal to 4/8 HLA-matched (HLA-A, B, C
and DR loci) cord blood unit from the National Marrow Donor Program (NMDP)
The cord blood unit must contain a minimum TNC of at least 1.8 x 10^9 and at least
8x10^7/kg TNC and at least 8 x 10^6 CD34+ cells (all doses prior to thawing). The
CBU will have undergone volume reduction (both plasma and red blood cell depletion)
prior to cryopreservation. All CBUs should be procured from public banks that meet
local applicable regulations
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

ECOG performance status of 2 or more
Major anticipated illness or organ failure incompatible with survival from transplant
HIV positive
Diagnosis of Fanconi s anemia (by chromosome breakage study)
Left ventricular ejection fraction < 40% (evaluated by ECHO)
Serum bilirubin >4 mg/dl
-Transaminases > 5x upper limit of normal
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
Availability of an HLA identical or 9/10 HLA matched (HLA A, B, C, DR, and DQ loci) -
relative to serve as a stem cell donor
The patient is deemed to be a candidate for a 10/10 HLA matched unrelated stem cell
transplant (availability of a donor and resources required for such a 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
Diffusion capacity of carbon monoxide (DLCO) <40% predicted 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)
Creatinine clearance < 50 cc/min/BSAm^2 by 24-hour urine collection adjusted by body
surface area
Allergy to bovine, Gentamicin, or to any product which may interfere with the
Presence of donor-specific antibodies (DSA) to the umbilical cord blood unit and for
cohort 1, to the haplo-identical donor
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