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A Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies


Phase 2
18 Years
59 Years
Open (Enrolling)
Both
Leukemia, Myeloid, Acute, Acute Lymphoblastic Leukemia, Myelodysplasia, Leukemia, Myelogenous, Chronic, Lymphoma, Non-Hodgkin

Thank you

Trial Information

A Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

Transplant (Day 0) through Day +100

Safety Issue:

No

Principal Investigator

Sherif Farag, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

IU Simon Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

0812-15; IUCRO-0223

NCT ID:

NCT00862719

Start Date:

March 2009

Completion Date:

March 2014

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Acute Lymphoblastic Leukemia
  • Myelodysplasia
  • Leukemia, Myelogenous, Chronic
  • Lymphoma, Non-Hodgkin
  • 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

Name

Location
IU Simon Cancer Center Indianapolis, Indiana  46202