A Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies
Umbilical cord blood (UCB) is increasingly used as a source of stem cells for patients with
blood cancers who need an allogeneic stem cell transplant (a transplant with stem cells from
another person) but who have no suitably matched donors. The advantages of UCB are that (1)
it is associated with less risk of transmitting an infection from a donor, (2) it can be
more safely given even if not completely matched compared to bone marrow or blood stem
cells, and (3) it is much more quickly available than unrelated donor bone marrow or blood
stem cells. While more commonly used for transplantation in children, UCB is increasingly
being used in adults. However, because they are larger than children, the relatively smaller
stem cell dose in UCB is major limitation for transplantation in adults, and engraftment can
be delayed. This study is investigating whether the drug sitagliptin can be used to increase
and speed up engraftment in adults receiving UCB transplantation, overcoming the limitation
of small stem cell doses associated with umbilical cord blood.
Sitagliptin is a drug given in tablet form that has been recently approved by the Food and
Drug Administration (FDA) for the treatment of certain patients with diabetes mellitus (a
disease that results in high blood sugar). Sitagliptin has been given to both normal healthy
volunteers and diabetic patients and has been found to be safe and well-tolerated. The drug
improves control of blood sugar in diabetics by inhibiting an enzyme called "CD26/DPP-IV."
Recent studies at Indiana University (and other centers) have shown that this same enzyme
plays an important role in the way transplanted stem cells find their way to the bone marrow
and engraft. Transplant studies in mice have found that inhibiting CD26/DPP-IV significantly
increases the engraftment of stem cells. Based on these studies, it is believed that drugs
that inhibit CD26/DPP-IV, such as sitagliptin, may also increase engraftment in patients who
receive clinical stem cell transplants.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Evaluate the efficacy of CD26/DPP-IV inhibition in increasing the proportion of adult patients with hematological malignancies engrafting by day +30 following transplantation of UCB by 30 percent.
Transplant (Day 0) through Day +100
Sherif Farag, MD, PhD
IU Simon Cancer Center
United States: Institutional Review Board
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