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Multicenter Phase II of CD26 Using Sitagliptin for Engraftment After UBC Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01720264
First Posted: November 2, 2012
Last Update Posted: April 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Sherif S. Farag, Indiana University
  Purpose
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).

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter 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 Sherif S. Farag, Indiana University:

Primary Outcome Measures:
  • The percent of subjects engrafting by day +30 after transplantation [ Time Frame: Day 0 to Day +30 post transplant ]
    The primary objective of this phase II study is to determine if systemic inhibition of CD26 can result in neutrophil engraftment in 70% or more of patients by day +30 after transplantation, with a rate of <50% considered unacceptable.


Secondary Outcome Measures:
  • Time to neutrophil engraftment [ Time Frame: Day 0 until first consecutive 3 days with ANC >/= 0.5 x 10^9/L ]
  • Time to platelet engraftment [ Time Frame: Day 0 until first consecutive 7 days where platelet count is >/= 20 x 10^9/L ]
  • Number of subjects with primary graft failure [ Time Frame: Day 0 to Day +100 ]
    Graft failure is defined as lack of neutrophil engraftment by Day +100 after transplantation in patients surviving a minimum of 14 days.

  • Number of subjects with Grade 3 and 4 non-hematological toxicities [ Time Frame: Day 0 to end of study ]
    Non-hematological toxicity will be graded and described according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  • Number of subjects with acute GvHD at Day +100 [ Time Frame: Day 0 to Day +100 ]
    Acute Graft versus Host Disease will be based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptome (Stage 0-4 for each organ).

  • Number of subjects with chronic GvHD at 1 year post transplant [ Time Frame: Day 0 to 1 year post transplant ]
    Chronic Graft versus Host Disease will be based on Filipovich et al. consensus document (BB&MT 2005) and Akpek et al. chronic GvHD grading system article (Blood 2003).

  • Grade of acute GvHD at 1 year post transplantation. [ Time Frame: Day 0 to 1 year post transplantation ]
    Acute Graft versus Host Disease will be based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms (Stage 0-4 for each organ).

  • Grade of chronic GvHD at Day +100 [ Time Frame: Day 0 to Day +100 ]
    Chronic Graft versus Host Disease will be based on Filipovich et al. consensus document (BB&MT 2005) and Akpek et al. chronic GVHD grading system (Blood 2003).

  • Grade of chronic GvHD at 1 year post transplantation [ Time Frame: Day 0 to 1 year post transplantation ]
    Chronic Graft versus Host Disease will be based on Filipovich et al. consensus article (BB&MT 2005) and Akpek et al. chronic GVHD grading system article (Blood 2003).

  • Number of subjects with acute GvHD at 1 year post transplantation [ Time Frame: Day 0 to 1 year post transplantation ]
    Acute Graft versus Host Disease will be based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptome (Stage 0-4 for each organ).

  • Number of subjects with chronic GVHD at Day 100. [ Time Frame: Day 0 to Day +100 ]
    Chronic Graft versus Host Disease will be based on Filipovich et al. consensus article (BB&MT 2005) and Akpek et al. chronic GVHD grading system (Blood 2003).

  • Grade of acute GvHD at Day +100 [ Time Frame: Day 0 to +100 ]
    Acute Graft versus Host Disease will be based on the modified Keystone Grading Scale for skin, liver and gastrointestinal symptoms (stage 0-4 for each organ).

  • Number of subjects with transplant-related mortality at 6 months post transplant [ Time Frame: Day 0 to 6 months post transplant ]
  • Time to disease relapse [ Time Frame: Day 0 until disease relapse ]
  • Time until death [ Time Frame: Day 0 until death ]
  • plasma levels of sitagliptin [ Time Frame: Baseline, 2, 4, 6 hrs after first dose; before 2nd dose on Day -1; before first daily dose on Day 0, +1, +2, +3; before last dose and 2, 4, 6, 12, 24 after last dose. ]
  • Percent inhibition of DPP-IV relative to baseline [ Time Frame: Baseline, 2, 4, 6 hrs after first dose; before 2nd dose on Day -1; before first daily dose on Day 0, +1, +2, +3; 24 hours after last dose. ]

Enrollment: 19
Actual Study Start Date: November 2, 2012
Estimated Study Completion Date: November 30, 2018
Estimated Primary Completion Date: November 30, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
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.
Drug: Sitagliptin
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.
Other Name: Januvia

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01720264


Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New York
New York Medical College/Westchester Medical Center/Maria Fareri Children's Hosptial
Valhalla, New York, United States, 10595
Sponsors and Collaborators
Sherif S. Farag
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Sherif S Farag, MBBS, PhD Indiana University
  More Information

Responsible Party: Sherif S. Farag, Lawrence H. Einhorn Professor of Oncology, Indiana University
ClinicalTrials.gov Identifier: NCT01720264     History of Changes
Other Study ID Numbers: 1208009261; HL112669
1R01HL112669-01 ( U.S. NIH Grant/Contract )
First Submitted: October 30, 2012
First Posted: November 2, 2012
Last Update Posted: April 11, 2017
Last Verified: April 2017

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