NCT05895201

High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Sitagliptin for the Prevention of GVHD

Phase I/II Trial of High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Sitagliptin for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Indiana University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label Phase I-II study to determine the safe doses of bortezomib, sitagliptin, and PTCy (Phase I) with expansion into a phase II trial to determine efficacy in improving survival.

Detailed description

Determine the safe doses of bortezomib, sitagliptin, and PTCy for use in expansion into a phase II trial. This is effectively the maximum tolerated dose of the drugs tested in a 3+3 design in a limited phase I portion. Phase I requires a maximum of 18 patients. Determine the efficacy of sitagliptin, bortezomib, and PTCy in improving the survival free of grade II-IV acute GVHD at day +100 from an expected 65% to 80% or more. This portion uses a Simon minimax two-stage design, testing the null hypothesis H0: p0 \< 0.65 versus the alternative hypothesis H1: p1 ≥ 0.8, where p is the probability of being alive and without grade II-IV acute GVHD at day 100 after transplantation. Using a minimax optimal stage design with a one-sided type I error set to 0.05, and a type II error rate set to 0.2 (power 80%). In the first stage, 31 evaluable patients will be entered. If 20 or fewer are alive without acute grade II-IV GVHD (i.e., 11 or more develop acute grade II-IV GvHD) by day +100, the study will be stopped in favor of the null hypothesis. On the other hand, if more than 20 are alive without grade II-IV acute GVHD by day +100, and additional 24 patients will be enrolled for a total of 55 evaluable patients. In the final analysis, if more than 41 remain alive free of grade II-IV acute GVHD (i.e., only 14 or less have developed acute grade II-IV acute GVHD by day +100), the null hypothesis will be rejected, and will conclude that the combination used for prevention of moderate to severe GVHD is worthy of further study.

Conditions

• Bone Marrow Transplant Complications
• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia, Adult
• Myelodysplastic Syndromes
• Chronic Myelomonocytic Leukemia

Interventions

Type	Name	Description
DRUG	Sitagliptin	600 or 400 (or MTD) mg PO every 12 hours on days -1 to +14 depending on dose level assignment.
DRUG	Bortezomib	1.3 or 1.0 mg/m2 (or MTD) IV push 6 hours after graft infusion completion (day 0), and 72 hours thereafter depending on dose level assignment.
DRUG	Cyclophosphamide	50 mg/kg IV over 1 hour on days +3 and +4

Timeline

• Start date: 2023-11-01
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2023-06-08
• Last updated: 2024-04-29

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study