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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Indiana University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01720264
First received: October 30, 2012
Last updated: June 24, 2014
Last verified: June 2014
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Indiana University:

Primary Outcome Measures:
  • The percent of subjects engrafting by day +30 after transplantation [ Time Frame: Day 0 to Day +30 post transplant ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
  • Time to platelet engraftment [ Time Frame: Day 0 until first consecutive 7 days where platelet count is >/= 20 x 10^9/L ] [ Designated as safety issue: Yes ]
  • Number of subjects with primary graft failure [ Time Frame: Day 0 to Day +100 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
  • Time to disease relapse [ Time Frame: Day 0 until disease relapse ] [ Designated as safety issue: No ]
  • Time until death [ Time Frame: Day 0 until death ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: November 2012
Estimated Primary Completion Date: November 2015 (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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720264

Contacts
Contact: Lisa L Wood, RN 317-944-1781 llwood@iupui.edu
Contact: Sherif Farag, MBBS, PhD 317-278-0843 ssfarag@iupui.edu

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Lisa Wood, RN    317-944-1781    llwood@iupui.edu   
Contact: Sherif Farag, MBBS, PhD    317-274-0843    ssfarag@iupui.edu   
Principal Investigator: Sherif Farag, MBBS, PhD         
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Sherif S Farag, M.B.B.S., Ph.D. Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01720264     History of Changes
Other Study ID Numbers: 1208009261; HL112669, 1R01HL112669-01
Study First Received: October 30, 2012
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
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
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014