A Prospective Study of Optimal Cord Selection for Haplo-Cord Transplantation: Targeting the Inherited Paternal Antigen (IPA) and Matching for the Non-Inherited Maternal Antigen (NIMA)
This is a clinical trial for subjects with hematologic malignancies ( acute leukemia,
myeloproliferative disorders, lymphoma, myeloma) who are in need of a donor stem cell
transplant, and for whom an umbilical cord blood transplant is thought to be the best
option. As donors for allogeneic transplant, we typically try to use related family members,
such as brothers or sisters, or volunteer donors who are 'HLA matched', i.e. share similar
proteins on their cells. This study is for subjects for whom such a matched sibling donor or
a matched unrelated donor is not available.
For such subjects a commonly used transplant procedure is to use stem cells from one or two
umbilical cords (UCB) from a newborn. These umbilical cord blood grafts, despite not
completely matching the recipient, cause few problems with graft vs host disease (a common
complication of transplant). But they tend to grow very slowly and subjects often have very
prolonged hospital stays and are at high risk for complications due to low blood counts.
Umbilical cord blood transplant will be the standard arm for this protocol.
This study uses a new method of bone marrow transplantation called combined haplo-identical
cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares
half of the HLA proteins ( haplo-identical) are collected from the blood, as well as cells
from an umbilical cord, and then both are transplanted. It is hoped that by using cells from
a haplo-identical relative, subjects will have a faster recovery and require fewer
transfusions. Over time the haplo-identical cells from the relative are replaced by the
cells from the cord blood. The combined transplantation of haplo-identical stem cells and
cord blood has previously been used in approximately 60 subjects with very encouraging
Traditionally it has been felt that the most important determinant of outcome of an UCB stem
cell transplant is the cord blood cell dose. The second determinant is the degree of
matching between donor and recipient. Many times, we have difficulty identifying UCB units
of sufficient cell dose that are well matched. Of interest,in our prior study of
haplo-cord SCT indicated outcomes seemed independent of the UCB cell dose. If this
preliminary observation is correct, we may be able to improve the outcomes of haplo cord
transplant further by accepting lower threshold UCB doses and rather focusing on optimal
matching (including matching for HLA and another characteristic called IPA). This is the
primary objective of this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Lowest threshold of umbilical cord nucleated cell dose for haplo-cord transplants.
We aim to identify the lowest threshold of umbilical cord nucleated cell dose that can be utilized assure durable umbilical cord blood engraftment in the haplo-cord transplants. The threshold will be defined as the lowest dose which assures cord blood engraftment occurs in at least 80% of subjects.
Koen van Besien, MD, PhD
Weill Medical College of Cornell University
United States: Food and Drug Administration
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