Acute Lymphoid Leukemia, Acute Myeloid Leukemia, Hematopoetic Myelodysplasia, Leukemia, Myelogenous, Chronic, Lymphoma, Non-Hodgkin
Conditions
Brief summary
The main purpose of this trial is to assess the efficacy and safety of sitagliptin in enhancing engraftment following umbilical cord blood transplantation (recovery of blood counts after transplant).
Detailed description
Umbilical cord blood (UCB) is more commonly used for transplantation in children but is being used in adults more often. However, because adults 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 trying to find out if the drug sitagliptin can be used to increase and speed up engraftment in adults receiving UCB transplantation.
Interventions
DRUGSitagliptin
Sitagliptin q 12 hours PO starting on Day -1 then given every 12 hours (total 10 doses) on Day 0, Day +1, +2 and Day +3.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Sherif S. Farag
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have one of the following disease types: * Acute myeloid leukemia (AML) with disease features as described in the protocol. * Acute lymphoblastic leukemia (ALL) with disease features as described in the protocol. * Myelodysplasia with disease features as described in the protocol. * Chronic myelogenous leukemia (CML) with disease features as described in the protocol. * Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the disease features as described in the protocol. * At least 35 days following start of preceding leukemia induction cytotoxic chemotherapy. * For patients in remission, there should be no readily available consenting HLA-matched related donor who is either matched fully matched or mismatched at only one locus of HLA-A, -B, and DRB1. * No availability of a readily available HLA-matched volunteer unrelated donor (8 of 8 allele match at HLA-A, -B, -C and -DRB1). * Patients must have a matched or partially matched UCB unit with \>/= 2.5 x10\^7 nucleated cells/kg of recipient weight at the time of cryopreservation. * No current uncontrolled bacterial, viral or fungal infection (defined as currently taking medication and progression of clinical symptoms). * No HIV disease. * Non pregnant and non-nursing. * Required baseline laboratory values as described in the protocol. * Signed written informed consent.
Exclusion criteria
* Symptomatic uncontrolled coronary artery disease or congestive heart failure. * Severe hypoxemia with room air PaO2\<70, supplemental oxygen dependence, or DLCO\<50% predicted. * Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy. * Prior allogeneic or autologous hematopoietic stem cell transplant in the last 6 months. * Patients who are taking other insulin secretagogues and/or insulin. * Patients who have hypersensitivity to sitagliptin. * Patients with a history of pancreatitis, cholelithiasis, alcoholism, or fasting hypertriglyceridemia (\> 2 x ULN).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent of Subjects Engrafting by Day +30 After Transplantation | Day 0 to Day +30 post transplant | Percent of patients and the 95% Binomial Confidence interval who were able to achieve neutrophils engraftment (defined as the date of the first of three consecutive ANC values obtained on different days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l) by 30 days following transplant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment | Transplant (Day 0) up to 1 year | 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 surviving at least 14 days after transplant will be evaluable for this endpoint. 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. |
| Time to Platelet Engraftment | Transplant (Day 0) up to 1 year | 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 three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided. |
| Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities | Day 0 up to 3 years | Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater. |
Countries
United States
Participant flow
Recruitment details
The study was stopped at 15 patients due to poor accrual. One patient subsequently found not to have met eligibility because she commenced treatment one day earlier than the prescribed 35-day interval from previous therapy is included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Post-transplant (Day 16) to 1 Year | Death | 8 |
| Post-transplant (Day 16) to 1 Year | Disease Progression | 4 |
| Transplant With Sitagliptin for 15 Days | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Sitagliptin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 40.9 years STANDARD_DEVIATION 13.96 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 9 / 15 |
Outcome results
Primary
The Percent of Subjects Engrafting by Day +30 After Transplantation
Percent of patients and the 95% Binomial Confidence interval who were able to achieve neutrophils engraftment (defined as the date of the first of three consecutive ANC values obtained on different days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l) by 30 days following transplant.
Time frame: Day 0 to Day +30 post transplant
Population: All patients who received treatment and were followed after transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | The Percent of Subjects Engrafting by Day +30 After Transplantation | 100 percentage of participants |
Secondary
Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities
Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.
Time frame: Day 0 up to 3 years
Population: All patients enrolled and received treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin | Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities | 0 Participants |
Secondary
Time to Neutrophil Engraftment
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 surviving at least 14 days after transplant will be evaluable for this endpoint. 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.
Time frame: Transplant (Day 0) up to 1 year
Population: All patients who received treatment and survived at least 14 days after transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin | Time to Neutrophil Engraftment | 19 days |
Secondary
Time to Platelet Engraftment
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 three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
Time frame: Transplant (Day 0) up to 1 year
Population: All patients who received treatment and who achieved platelet recovery/engraftment of platelets.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitagliptin | Time to Platelet Engraftment | 52 days |