Sitagliptin for the Treatment of Grade 3-4 and Refractory Acute Graft-versus-host Disease

NCT04448587 | Unknown Phase 2

• 1 other identifier: 0368-20
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The prognosis of severe (grade 3-4) and steroid refractory acute graft-versus-host disease (GVHD) continues to be dismal. Sitagliptin given as GVHD-prophylaxis has recently been shown to reduce the incidence of acute GVHD to less than 10% with an excellent safety profile. In this single center and single arm phase 2 study we aim to explore the safety and efficacy of sitagliptin in the treatment of severe and refractory acute GVHD. Patient with new onset grade 3-4 acute GVHD will receive standard treatment consisting CNI and methylprednisolone 1-2 mg/kg/day or an equivalent dose of prednisone. Patients with refractory grade 2-4 acute GVHD will continue their current treatment; however methylprednisolone dose will be reduced to ≤ 1 mg/kg/day or an equivalent dose of prednisone. Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100 mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug related side effects or drug intolerance, the last tolerated dose will be resumed. Patients responding well to lower doses of sitagliptin, will not be given higher doses of the drug. Sitagliptin will be provided as long as deemed effective by the treating physician up to three months. The primary end point will be the proportion of patients achieving complete remission(CR), very good partial response (VGPR) or partial response (PR) by day 28.

Conditions

Graft Vs Host Disease

Keywords

SITAGLIPTIN

Outcome Measures

Primary Outcomes (1)

• Response

  proportion of patients achieving complete remission (CR), very good partial response (VGPR) or partial response (PR) by day 28.

  day 28

Secondary Outcomes (4)

• Incidence of treatment-emergent adverse events (safety and tolerability)

  3 months

• Response

  day 56

• Response

  6 months

• Biomarker profile

  By days 0, 14, 28, 42, 56, 70, 100

Study Arms (1)

Sitagliptin

EXPERIMENTAL

Drug: Sitagliptin 100mg

Interventions

Sitagliptin 100mg DRUG

Oral sitagliptin will be commenced at a dose of 100 mg BID. The dose will be increased by 100 mg every three days up to a maximal dose of 300 mg BID. In the case of significant drug related side effects or drug intolerance, the last tolerated dose will be resumed. Patients responding well to lower doses of sitagliptin, will not be given higher doses of the drug. Sitagliptin will be provided as long as deemed effective by the treating physician up to three months.

Also known as: JANUVIA

Sitagliptin

Eligibility Criteria

• Age: 17 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18-year old
• Grade 3-4 acute GVHD
• Refractory grade 2-4 acute GVHD
• Signed informed consent.
• Complete remission of the disease for which the patient was transplanted for.

You may not qualify if:

• Patients with diabetes mellitus requiring therapy with oral hypoglycemic medications or Insulin on top of sitagliptin.
• Serious hypersensitivity reaction to sitagliptin such as angioedema or anaphylaxis.

Sponsors & Collaborators

• Rabin Medical Center: lead

Study Sites (1)

Rabin Medical Center

Petah Tikva, Israel

RECRUITING

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

Central Study Contacts

Moshe Yeshurun, MD

CONTACT

972-52-6015543; moshey@clalit.org.il

Liat Shragian-Alon, MD

CONTACT

972-54-2394930; LIATSHR@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head BMT Unit

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: June 26, 2020
• Study Start: October 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: February 2, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)