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

Graft Vs Host Disease Clinical Trial

— GVHD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04448587
• Other study ID #: 0368-20
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2021
• Source: Rabin Medical Center
• Contact: Moshe Yeshurun, MD
• Phone: 972-52-6015543
• Email: moshey[@]clalit.org.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The prognosis of severe (grade 3-4) and steroid refractory acute 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 CR, VGPR or PR by day 28. The secondary endpoints will be safety profile, proportion of patients achieving CR, VGPR or PR by day 56, 6-month duration of response (time from first response to GVHD progression or death), proportion of patients discontinuing immunosuppressive treatment by 3 and 6 months, proportion of patients developing chronic GVHD (limited and extensive) by 6 months, time to response, specific organ response, biomarker profile (ST2 and REG3a), Infection profile, OS at 6 months, GVHD free - disease free survival at 6 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Graft Vs Host Disease

Intervention

Drug:
• Sitagliptin 100mg
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.

Locations

Country	Name	City	State
Israel	Rabin Medical Center	Petach Tikva

Sponsors (1)

Lead Sponsor	Collaborator
Rabin Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response	proportion of patients achieving complete remission (CR), very good partial response (VGPR) or partial response (PR) by day 28.	day 28
Secondary	Incidence of treatment-emergent adverse events (safety and tolerability)	Incidence of treatment-emergent adverse events (safety and tolerability)	3 months
Secondary	Response	Proportion of patients achieving CR, VGPR or PR by day 56.	day 56
Secondary	Response	GVHD free - disease free survival at 6 months	6 months
Secondary	Biomarker profile	ST2 and REG3a blood levels	By days 0, 14, 28, 42, 56, 70, 100