Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

NCT02683525 | Completed Phase 2 Results DMC

• 1 other identifier: IUSCC-0522
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective Evaluate the efficacy of sitagliptin in reducing the incidence of grade II-IV acute Graft Versus-Host Disease (GvHD) by day +100 post-transplant in patients undergoing allogeneic hematopoietic stem cell transplantation and receiving standard sirolimus and tacrolimus GvHD prophylaxis. Secondary Objectives The following descriptive secondary objectives will be studied:

1. 1.Describe the tolerability and potential toxicity of sitagliptin.
2. 2.Describe the cumulative incidence of grades II-IV acute GvHD by day +100.
3. 3.Describe the cumulative incidence of grades III-IV acute GvHD.
4. 4.Describe the engraftment kinetics of absolute neutrophil count and platelets.
5. 5.Describe the incidence of infections occurring during the 100 days post-transplant.
6. 6.Describe non-relapse mortality (NRM) at day +30, +100, and 1 year post-transplant.
7. 7.Describe overall survival.
8. 8.Describe the incidence of chronic GvHD.
9. 9.Describe the cumulative incidence of relapse of the primary hematological malignancy.

Conditions

Graft vs Host Disease; Hematopoietic Stem Cell Transplantation

Keywords

Allogeneic; Sitagliptin

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Grade II-IV Acute GvHD by Day +100 Following Transplant

  Percent of patients and the 95% Confidence interval who did not have Grade II-IV Acute GvHD by 100 days following transplant. Since the study completed the two-phase design, proper inference was used to generate the confidence interval (Koyama and Chen). Only patients who were on the study for at least 100 days post transplant were included in the analysis.

  up to 100 days

Secondary Outcomes (10)

• Percentage of Patients With Grade II-IV Acute GvHD at Day +100

  100 days from transplant

• Number of Patients With Treatment Related Adverse Events Grade 3 or Higher for Non-hematological Toxicity

  up to 2 months

• Percentage of Patients With Grade III-IV Acute GvHD at Day +100

  100 days from transplant

• Median Time to Engraftment of Neutrophils

  up to 1 month

• Median Time to Engraftment of Platelets

  up to 4 months

Study Arms (1)

Sitagliptin

EXPERIMENTAL

Sitagliptin 600 mg q 12 hours PO starting on Day -1 before transplant to be administered between 8:00 am and 10:00 am then given every 12 hours (total 32 doses) through day +14.

Drug: Sitagliptin

Interventions

Sitagliptin DRUG

600 mg ever 12 hours by mouth will be given starting the day before transplant through day +14 after transplant

Sitagliptin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A. Patients with any of the following hematologic malignancies:
• Acute myeloid leukemia (AML) with any of the following:
• In first remission (CR1) with intermediate risk or high-risk cytogenetic and/or molecular features.
• Patients in second or subsequent complete remission (CR2, CR3, etc.).
• Primary refractory or relapsed AML with no more than any one of the following adverse additional features according to modified CIBMTR criteria:49
• Duration of first CR \< 6 months
• Poor risk cytogenetics or molecular features (FLT-3 internal tandem duplication (ITD); complex karyotype with ≥3 clonal abnormalities, 5q-/-5, 7q-/-7, 11q23 abnormalities, inv(3), monosomal karyotype)
• Circulating peripheral blood blasts at time of enrollment
• Karnofsky performance status \<90%
• Acute lymphoblastic leukemia (ALL) with any of the following:
• In CR1 or subsequent complete remission (CR2, CR3, etc.)
• Primary refractory or relapsed ALL with no more than one of the following adverse features according to modified CIBMTR criteria:49
• Second or subsequent relapse
• Bone marrow blasts \>25% at time of enrollment
• Age \>40 years

You may not qualify if:

• A. Symptomatic uncontrolled coronary artery disease or congestive heart failure
• B. Severe hypoxemia with room air PaO2 \< 70, supplemental oxygen dependence, or DLCO \< 50% predicted
• C. Patients with active central nervous system involvement
• D. Prior allogeneic or autologous hematopoietic stem cell transplant in past 12 months
• E. Patients with diabetes mellitus requiring insulin secretagogues and/or insulin
• F. Patients with hypertriglyceridemia with serum triglyceride level ≥500 mg/d (lipid lowering drugs may be used to control level)
• G. Patients with a history of pancreatitis
• H. Patients with symptomatic cholelithiasis
• I. Patients with a current dependence on alcohol (characterized by a physical addiction to alcohol that interferes with physical or mental health, and social, family or job responsibilities)

Sponsors & Collaborators

• Sherif S. Farag: lead

Study Sites (2)

Indiana University Health Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• Farag SS, Abu Zaid M, Schwartz JE, Thakrar TC, Blakley AJ, Abonour R, Robertson MJ, Broxmeyer HE, Zhang S. Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. N Engl J Med. 2021 Jan 7;384(1):11-19. doi: 10.1056/NEJMoa2027372.

  PMID: 33406328 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Dr. Sherif Farag
• Organization: IndianaU

ssfarag@iu.edu

(317) 278-0460

Study Officials

• Sherif Farag, MD, PhD

  Indiana University School of Medicine, Indiana University Simon Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Lawrence H. Einhorn Professor of Oncology

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 17, 2016
• Study Start: February 3, 2016
• Primary Completion: February 13, 2019
• Study Completion: October 1, 2019
• Last Updated: January 22, 2021
• Results First Posted: December 29, 2020

Record last verified: 2021-01

Locations

US (2)