Enhancing Engraftment of Cord Blood by CD26 Inhibition

Project: Research project

Description

DESCRIPTION (provided by applicant): Cord blood (CB) transplantation has greatly extended availability of a hematopoietic cell transplant (HCT) to patients who would not otherwise have received this curative treatment. CB has several advantages over bone marrow (BM) and mobilized peripheral blood (mPB), including ease and safety of collection, ready availability, and lessened acute and chronic graft vs. host disease (GVHD). However, a disadvantage with CB is low numbers of nucleated cells, hematopoietic progenitors (HPC), and likely stem cells (HSC), compared with BM or mPB, which has translated into increase risk of graft failure, delayed engraftment, and delayed immune reconstitution. Based on our published laboratory and preclinical animal model studies, preliminary clinical data, and mechanistic studies on CD26/Dipeptidylpeptidase (DPP) IV activities reported herein, we believe that inhibition of CD26/DPPIV will significantly enhance engraftment capability of limiting numbers of human CB cells, and accelerate time to engraftment of single CB units. This multi-PI grant proposes the following specific aims: Aim 1: Conduct a multicenter phase II clinical trial to assess efficacy and safety of systemic inhibition of CD26/DPPIV using sitagliptin, to enhance engraftment of single CB units in adults with hematological cancers. Hypothesis: Inhibition of CD26/DPPIV by systemic administration of CD26 inhibitor sitagliptin will enhance engraftment, without negatively impacting relatively lower levels of GVHD associated with single CB transplantation. Primary Objective: Evaluate proportion of patients with neutrophil recovery by day +30 after transplant as a measure of speed of engraftment. Using an optimal two-stage design,
StatusFinished
Effective start/end date3/1/122/28/17

Funding

  • National Institutes of Health: $720,286.00
  • National Institutes of Health: $760,603.00
  • National Institutes of Health: $727,047.00
  • National Institutes of Health: $716,107.00
  • National Institutes of Health: $720,299.00

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Fetal Blood
Transplants
Transplantation
Bone Marrow
Safety
Phase II Clinical Trials
Organized Financing
Hematopoietic Stem Cells
Blood Cells
Neutrophils
Stem Cells
Animal Models
Neoplasms

ASJC

  • Medicine(all)