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

Study Overview
=================
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: Collect peripheral blood stem cells (PBSCs) from donors for transplant. Determine the largest possible dose of bortezomib that can be given to recipients with various blood cancers in a safe manner. Monitor the recipient for risk of infection or side affects associated with the transplant. Monitor the recipient for increased immunity following transplantation.

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

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

Intervention / Treatment
-----------------
* Drug: Tacrolimus
* Drug: Sirolimus
* Drug: Bortezomib


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|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)|
|Drug: 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)|
|Drug: 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|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tacrolimus, Sirolimus, Bortezomib, Acute Graft Versus Host Disease, Allogeneic Peripheral Blood Stem Cell Transplantation