2025-12-12 アメリカ国立衛生研究所(NIH)
<関連情報>
- https://www.nih.gov/news-events/news-releases/expanded-umbilical-cord-blood-transplant-achieves-94-survival-severe-aplastic-anemia-patients
- https://clinicaltrials.gov/study/NCT03173937
重症再生不良性貧血および低形成性MDSに対する非血縁者間臍帯血移植:臍帯血由来体外増殖幹細胞および前駆細胞であるCordIn™を用いて、生着を促進し、移植結果を改善する。 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.
ClinicalTrials.gov ID NCT03173937
Sponsor National Heart, Lung, and Blood Institute (NHLBI)
Information provided by National Institutes of Health Clinical Center (CC) (National Heart, Lung, and Blood Institute (NHLBI)) (Responsible Party)
Last Update Posted 2025-11-24
Study Overview
Brief Summary
Background:
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.
Objective:
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.
Eligibility:
Recipients ages 4-60 with SAA or MDS
Donors ages 4-75
Design:
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
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 or biosimilar (G-CSF) 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.
Detailed Description
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 percent 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 cells ( (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 cells. 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 10^6 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.
