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

Updated on 22 December 2020
myelodysplastic syndromes
myelodysplastic syndrome (mds)
anemia studies
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 4-55 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:
    • 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.

Please visit our Patient Recruitment Page for more information.



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.


Please visit our Patient Recruitment Page for more information.

Condition Aplastic Anemia, Aplastic Anemia, Anemia; Non-Small-Cell Lung Cancer, Myelodysplastic Syndromes (MDS), Severe Aplastic Anemia Hypo-Plastic MDS Pediatric Adult
Clinical Study IdentifierTX218205
Last Modified on22 December 2020


Yes No Not Sure

Inclusion Criteria

Diagnosed with severe aplastic anemia characterized by all of the following
Bone marrow cellularity <30% (excluding lymphocytes)
Transfusion dependence for platelets and/or RBCs
Neutropenia [(absolute neutrophil count <= 1000 cells/ uL) OR for patients receiving granulocyte transfusions, absolute neutrophil count <= 1000 cells/ uL 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
Intolerance of or failure to respond to standard immunosuppressive therapy
Identification of at least one HLA- haploidentical (i.e. greater than or equal to 5/10 and less than or equal to 8/10 HLA match) related donor (HLA-A, B, C, DR, and DQ loci) who is available to serve as a haploidentical stem cell donor for a salvage haplo-transplant in the event that the Cordin unit has been rejected (cohort 1 only)
Availability of at least one 5/8 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 1.8x10^7/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
Ages 4-55 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

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)
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% 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)
Left ventricular ejection fraction < 40% (evaluated by ECHO)
Transaminases > 5x upper limit of normal
Serum bilirubin >4 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
Allergy to bovine, Gentamicin, or to any product which may interfere with the treatment
Presence of donor-specific antibodies (DSA) to the umbilical cord blood unit and for cohort 1, to the haplo-identical donor
CELLS (cohort 1 only)
HLA mismatched family donor ( greater than or equal to 5/10 and less than or equal to 8/10 HLA match (HLA-A, B, C, DR, and DQ loci)) who is available to donate CD34+ cells
Ages 4-75 inclusive. Note: a pediatric family member will only be considered as a donor if a suitable adult haplo-identical donor is not available
Weight greater than or equal to 15 kg
For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian who is not the recipient of the transplant and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend
Genetic testing for genes associated with bone marrow failure syndromes (BMFS) perfomed at a CLIA-certified laboratory.If there is a suspicion of familial BMFS in the recipient, then the haplo donor must have undergone genetic testing for genes associated with BMFS - performed at a CLIA-certified laboratory, prior to enrolling in this protocol (applies only to cohort 1)
Pregnant or lactating
A pediatric haplo-identical donor will be excluded if a suitable adult haplo-identical donor is available
Unfit to receive filgrastim (G-CSF) and undergo apheresis (history of stroke, MI, unstable angina, uncontrolled hypertension, severe heart disease or palpable spleen)
HIV positive (Donors who are positive for HBV, HCV or HTLV-I/II, T.cruzi (Chagas) may be used at the discretion of the investigator following counseling and approval from the recipient)
Sickling hemoglobinopathies including HbSS or HbSC. Donors with HbAS are acceptable
Psychiatric illness that would limit the patient s ability to tolerate and/or comply with study requirements
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