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Sitagliptin Umbilical Cord Blood Transplant Study

I

Indiana University School of Medicine

Status and phase

Completed
Phase 2

Conditions

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

Treatments

Drug: Sitagliptin

Study type

Interventional

Funder types

Other

Identifiers

NCT00862719
0812-15 IUCRO-0223;

Details and patient eligibility

About

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).

Full 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.

Enrollment

29 patients

Sex

All

Ages

18 to 59 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

29 participants in 3 patient groups

Sitagliptin once per day
Experimental group
Description:
600 mg sitagliptin once per day orally starting on Day -1 for a total of 4 doses
Treatment:
Drug: Sitagliptin
Sitagliptin twice per day
Experimental group
Description:
600 mg sitagliptin twice per day orally starting on Day -1 for a total of 8 doses
Treatment:
Drug: Sitagliptin
Sitagliptin three times per day
Experimental group
Description:
600 mg sitagliptin three times per day orally starting on Day -1 for a total of 12 doses
Treatment:
Drug: Sitagliptin

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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