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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00670423

Enrollment

Registered

2008-05-01

Start date

2008-05-16

Completion date

2013-10-16

Last updated

2018-08-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Tacrolimus, Sirolimus, Bortezomib, Acute Graft Versus Host Disease, Allogeneic Peripheral Blood Stem Cell Transplantation

Brief 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.

Interventions

DRUGTacrolimus

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)

DRUGSirolimus

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)

DRUGBortezomib

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
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

Measure	Time frame
To assess the toxicity of bortezomib	Baseline through end of study
To describe engraftment	Baseline through end of study
To describe the incidence of acute and chronic GVHD	Baseline through end of study

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026