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Sitagliptin Umbilical Cord Blood Transplant Study

Primary Purpose

Leukemia, Myeloid, Acute, Acute Lymphoblastic Leukemia, Myelodysplasia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sitagliptin
Sponsored by
Indiana University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have one of the following disease types with disease-specific features as outlined in the protocol:

    • Acute myeloid leukemia (AML)
    • Acute lymphoblastic leukemia (ALL)
    • Myelodysplasia
    • Chronic myelogenous leukemia
    • 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
    • Hodgkin's lymphoma
    • Relapsed Multiple Myeloma
  • At least 35 days following start of preceding leukemia induction cytotoxic chemotherapy
  • Patient age 18-55 years
  • Karnofsky Performance status ≥ 70%
  • No availability of a 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 with unstable disease who are in danger of significant disease progression while waiting to procure volunteer donor cells will be eligible to be treated on this protocol, even if a matched donor is available.
  • Patients must have a matched or partially matched UCB unit with greater than 1.8 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. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.
  • Non pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks.
  • Required baseline laboratory values as defined in the protocol

Exclusion Criteria:

  • Symptomatic uncontrolled coronary artery disease or congestive heart failure.
  • Severe hypoxemia with room air PaO2 less than 70, supplemental oxygen dependence, or DLCO less than 50 percent 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

Sites / Locations

  • IU Simon Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Sitagliptin once per day

Sitagliptin twice per day

Sitagliptin three times per day

Arm Description

600 mg sitagliptin once per day orally starting on Day -1 for a total of 4 doses

600 mg sitagliptin twice per day orally starting on Day -1 for a total of 8 doses

600 mg sitagliptin three times per day orally starting on Day -1 for a total of 12 doses

Outcomes

Primary Outcome Measures

Cumulative Incidence of Patients With Engraftment by Day +30 Following Transplant
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.

Secondary Outcome Measures

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 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 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
Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.

Full Information

First Posted
March 16, 2009
Last Updated
August 25, 2016
Sponsor
Indiana University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00862719
Brief Title
Sitagliptin Umbilical Cord Blood Transplant Study
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
February 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University School of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this trial is to study whether the drug sitagliptin can be given safely to patients undergoing umbilical cord blood transplantation to speed up engraftment (recovery of blood counts after transplant).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Acute Lymphoblastic Leukemia, Myelodysplasia, Leukemia, Myelogenous, Chronic, Lymphoma, Non-Hodgkin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sitagliptin once per day
Arm Type
Experimental
Arm Description
600 mg sitagliptin once per day orally starting on Day -1 for a total of 4 doses
Arm Title
Sitagliptin twice per day
Arm Type
Experimental
Arm Description
600 mg sitagliptin twice per day orally starting on Day -1 for a total of 8 doses
Arm Title
Sitagliptin three times per day
Arm Type
Experimental
Arm Description
600 mg sitagliptin three times per day orally starting on Day -1 for a total of 12 doses
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia
Intervention Description
600 mg sitagliptin taken orally per the schedule listed in each of the three separate arms.
Primary Outcome Measure Information:
Title
Cumulative Incidence of Patients With Engraftment by Day +30 Following Transplant
Description
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 Frame
Transplant (Day 0) through Day +30
Secondary Outcome Measure Information:
Title
Time to Neutrophil Engraftment
Description
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 Frame
Transplant (Day 0) up to 1 year
Title
Time to Platelet Engraftment
Description
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.
Time Frame
Transplant (Day 0) up to 1 year
Title
Treatment Related Adverse Events Grade 3 or Higher for Non-hematological Toxicity
Description
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
Transplant (Day 0) up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have one of the following disease types with disease-specific features as outlined in the protocol: Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Myelodysplasia Chronic myelogenous leukemia 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 Hodgkin's lymphoma Relapsed Multiple Myeloma At least 35 days following start of preceding leukemia induction cytotoxic chemotherapy Patient age 18-55 years Karnofsky Performance status ≥ 70% No availability of a 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 with unstable disease who are in danger of significant disease progression while waiting to procure volunteer donor cells will be eligible to be treated on this protocol, even if a matched donor is available. Patients must have a matched or partially matched UCB unit with greater than 1.8 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. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies. Non pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks. Required baseline laboratory values as defined in the protocol Exclusion Criteria: Symptomatic uncontrolled coronary artery disease or congestive heart failure. Severe hypoxemia with room air PaO2 less than 70, supplemental oxygen dependence, or DLCO less than 50 percent 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherif Farag, MD, PhD
Organizational Affiliation
IU Simon Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
IU Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23270493
Citation
Farag SS, Srivastava S, Messina-Graham S, Schwartz J, Robertson MJ, Abonour R, Cornetta K, Wood L, Secrest A, Strother RM, Jones DR, Broxmeyer HE. In vivo DPP-4 inhibition to enhance engraftment of single-unit cord blood transplants in adults with hematological malignancies. Stem Cells Dev. 2013 Apr 1;22(7):1007-15. doi: 10.1089/scd.2012.0636. Epub 2013 Feb 15.
Results Reference
derived

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Sitagliptin Umbilical Cord Blood Transplant Study

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