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

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

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).

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin; Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Leukemia, Myelogenous, Chronic; Hematopoetic Myelodysplasia
• Intervention / Treatment: Drug: Sitagliptin

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College/Westchester Medical Center/Maria Fareri Children's Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Januvia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percent of Subjects Engrafting by Day +30 After Transplantation	Percent of patients and the 95% Binomial Confidence interval who were able to achieve neutrophils engraftment (defined as the date of the first of three consecutive ANC values obtained on different days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l) by 30 days following transplant.	Day 0 to Day +30 post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Neutrophil Engraftment	Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.	Transplant (Day 0) up to 1 year
Time to Platelet Engraftment	Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.	Transplant (Day 0) up to 1 year
Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities	Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.	Day 0 up to 3 years

Collaborators and Investigators

• Sponsor: Sherif S. Farag
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Sherif S Farag, MBBS, PhD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2012
• Primary Completion (Actual): August 27, 2016
• Study Completion (Actual): December 15, 2017

Study Registration Dates

• First Submitted: October 30, 2012
• First Submitted That Met QC Criteria: October 31, 2012
• First Posted (Estimate): November 2, 2012

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 17, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Lymphoma; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: 1208009261; HL112669; 1R01HL112669-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No