A Study Using Tacrolimus, Sirolimus and Bortezomib as Acute Graft Versus Host Disease (GVHD) Prophylaxis in Allogeneic Peripheral Blood Stem Cell (PBSC) Transplantation

Graft vs Host Disease Clinical Trial

Official title:

A Phase I Study Using Tacrolimus, Sirolimus and Bortezomib as Acute Graft Versus Host Disease Prophylaxis in Allogeneic Peripheral Blood Stem Cell (PBSC) Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670423
• Other study ID #: IUCRO-0204
• Secondary ID: 0803-17
• Status: Completed
• Phase: Phase 1
• Start date: May 16, 2008
• Est. completion date: October 16, 2013

Study information

• Verified date: August 2018
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is determine the highest dose of bortezomib, a new drug for graft-versus host disease prevention, that can be given in combination with sirolimus and Tacrolimus, without causing severe side effects. This research is being done because there is no treatment that is 100% effective in preventing graft versus host disease.

The goals of this study are to:

1. Collect peripheral blood stem cells (PBSCs) from donors for transplant.

2. Determine the largest possible dose of bortezomib that can be given to recipients with various blood cancers in a safe manner.

3. Monitor the recipient for risk of infection or side affects associated with the transplant.

4. Monitor the recipient for increased immunity following transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 16, 2013
• Est. primary completion date: July 5, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Undergoing myeloablative peripheral blood stem cell transplantation

• Have an HLA matched-related or matched-unrelated donor (9/10 antigen or allelic mismatch or 10/10 HLA match permitted).

• Hematological malignancy including patients with: AML, ALL, NHL, Hodgkin's Disease, CLL, CML, MDS and Multiple Myeloma

• Meeting institutional standard criteria for allogeneic PBSC transplantation

Exclusion Criteria:

• Patient has >Grade 2 peripheral neuropathy within 14 days before enrollment.

• History of autologous or allogeneic transplantation

• Evidence of HIV seropositivity

• Evidence of active infection

• Patients with cardiac dysfunction as described in the protocol

• Patients with hypersensitivity to bortezomib, boron or mannitol

Related Conditions & MeSH terms

• Graft vs Host Disease
• Peripheral Blood Stem Cell Transplantation
• Transplantation, Homologous

Intervention

Drug:
• Tacrolimus
Tacrolimus as a continuous IV infusion will begin on day -3. (Levels will be monitored at least every 3 days to target 5-10 ng/mL)
• Sirolimus
Sirolimus oral loading dose on day -3, followed by oral daily dose. (Levels will be monitored at least every 3 days to target 3-12 ng/mL)
• Bortezomib
Administered intravenously on day 0 (a minimum of 6 hours post-infusion of PBSC), and on day +3. The following dose levels will be used: Cohort 1 (3-6 pts): 1 mg/m2 on days 0 and +3 Cohort 2 (3-6 pts): 1.3 mg/m2 on days 0 and +3 Cohort 3 (3-10 pts): 1.6 mg/m2 on days 0 and +3

Locations

Country	Name	City	State
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Jennifer E. Schwartz	Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the maximum tolerated dose (MTD) of bortezomib in combination with tacrolimus and sirolimus as GVHD prophylaxis in patients undergoing myeloablative allogeneic peripheral blood stem cell transplantation.		Baseline through end of study
Secondary	To assess the toxicity of bortezomib		Baseline through end of study
Secondary	To describe engraftment		Baseline through end of study
Secondary	To describe the incidence of acute and chronic GVHD		Baseline through end of study