Sitagliptin Umbilical Cord Blood Transplant Study

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00862719
First received: March 16, 2009
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

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).


Condition Intervention Phase
Leukemia, Myeloid, Acute
Acute Lymphoblastic Leukemia
Myelodysplasia
Leukemia, Myelogenous, Chronic
Lymphoma, Non-Hodgkin
Drug: Sitagliptin
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • 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. [ Time Frame: Transplant (Day 0) through Day +100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Define the median times to neutrophil and platelet engraftment [ Time Frame: Day 0 through Day +100 ] [ Designated as safety issue: No ]
  • Describe rate of engraftment failure by day +100 [ Time Frame: Day 0 through Day +100 ] [ Designated as safety issue: No ]
  • Describe the incidence of grade 3 and 4 non-hematological toxicity [ Time Frame: Day 0 through Day +100 ] [ Designated as safety issue: Yes ]

Enrollment: 29
Study Start Date: March 2009
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin once per day, twice per day or three times per day.
Drug: Sitagliptin
  • 600 mg/day PO starting on Day -1 for a total of 4 doses.
  • 600 mg/bid PO starting on Day -1 for a total of 8 doses.
  • 600 mg/tid PO starting on Day -1 for a total of 12 doses.
Other Name: Januvia

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.

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00862719

Locations
United States, Indiana
IU Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Sherif Farag, MD, PhD IU Simon Cancer Center
  More Information

No publications provided by Indiana University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00862719     History of Changes
Other Study ID Numbers: 0812-15; IUCRO-0223
Study First Received: March 16, 2009
Last Updated: December 6, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Sitagliptin
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 14, 2014