Sitagliptin Umbilical Cord Blood Transplant Study
Leukemia, Myeloid, Acute
Acute Lymphoblastic Leukemia
Leukemia, Myelogenous, Chronic
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies|
- Cumulative Incidence of Patients With Engraftment by Day +30 Following Transplant [ Time Frame: Transplant (Day 0) through Day +30 ] [ Designated as safety issue: No ]Evaluate the efficacy of CD26/DPP-IV inhibition in increasing the cumulative incidence of adult patients with hematological malignancies engrafting by day +30 following transplantation of UCB by 30 percent. The cumulative incidence of patients achieving this will be reported. The value of the estimate will be from bootstrapping 1000 samples with replacement of the data and the 95% confidence interval will be calculated using the percentile method.
- Time to Neutrophil Engraftment [ Time Frame: Transplant (Day 0) up to 1 year ] [ Designated as safety issue: No ]Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided. For the RCD group, all patients engrafted before day +30, except one patient who died at day 28 before engraftment. For the PD group, all patients engrafted before day +100, except one patient who died on day +103 before engraftment. For the 600 mg sitagliptin/12 hours group, two patients engrafted before day +100, and the other two patients died before day +100 before engraftment. The one patient on 600 mg sitagliptin/8 hours died on day +14 before engraftment.
- Time to Platelet Engraftment [ Time Frame: Transplant (Day 0) up to 1 year ] [ Designated as safety issue: No ]Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
- Treatment Related Adverse Events Grade 3 or Higher for Non-hematological Toxicity [ Time Frame: Transplant (Day 0) up to 3 years ] [ Designated as safety issue: Yes ]Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.
|Study Start Date:||March 2009|
|Study Completion Date:||February 2015|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Sitagliptin once per day, twice per day or three times per day.
Other Name: Januvia
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00862719
|United States, Indiana|
|IU Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Sherif Farag, MD, PhD||IU Simon Cancer Center|