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

NCT00670423 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IUCRO-02040803-17
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Interventions

Tacrolimus DRUG

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)

Also known as: Prograf®

Sirolimus DRUG

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)

Also known as: Rapamune®

Bortezomib DRUG

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

Also known as: Velcade®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jennifer E. Schwartz: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Tacrolimus; Sirolimus; Bortezomib

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jennifer Schwartz, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: May 16, 2008
• Primary Completion: July 5, 2012
• Study Completion: October 16, 2013
• Last Updated: August 16, 2018

Record last verified: 2018-08

Locations

US (1)