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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tacrolimus

Sirolimus

Bortezomib

About this trial

This is an interventional treatment trial for Graft vs Host Disease focused on measuring Tacrolimus, Sirolimus, Bortezomib, Acute Graft Versus Host Disease, Allogeneic Peripheral Blood Stem Cell Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Indiana University Melvin and Bren Simon Cancer Center

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To assess the toxicity of bortezomib

To describe engraftment

To describe the incidence of acute and chronic GVHD

Full Information

NCT ID

NCT00670423

First Posted

April 29, 2008

Last Updated

August 14, 2018

Sponsor

Jennifer E. Schwartz

Collaborators

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00670423

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

May 16, 2008 (Actual)

Primary Completion Date

July 5, 2012 (Actual)

Study Completion Date

October 16, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Jennifer E. Schwartz

Collaborators

Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

Prograf®

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Other Intervention Name(s)

Rapamune®

Intervention Description

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)

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade®

Intervention Description

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

Primary Outcome Measure Information:

Title

Time Frame

Baseline through end of study

Secondary Outcome Measure Information:

Title

To assess the toxicity of bortezomib

Time Frame

Baseline through end of study

Title

To describe engraftment

Time Frame

Baseline through end of study

Title

To describe the incidence of acute and chronic GVHD

Time Frame

Baseline through end of study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer Schwartz, MD

Organizational Affiliation

Indiana University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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