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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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00670423
First received: April 29, 2008
Last updated: July 19, 2012
Last verified: July 2012
History of Changes
  Purpose

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.

Condition Intervention Phase
Graft vs Host Disease
Peripheral Blood Stem Cell Transplantation
Transplantation, Homologous
 Drug: Tacrolimus
Drug: Sirolimus
Drug: Bortezomib
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Indiana University:

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. [ Time Frame: Baseline through end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the toxicity of bortezomib [ Time Frame: Baseline through end of study ] [ Designated as safety issue: Yes ]
  • To describe engraftment [ Time Frame: Baseline through end of study ] [ Designated as safety issue: No ]
  • To describe the incidence of acute and chronic GVHD [ Time Frame: Baseline through end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 22
Study Start Date: May 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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)
    Other Name: Prograf®
    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)
    Other Name: Rapamune®
    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

    Other Name: Velcade®
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00670423

Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Jennifer Schwartz, MD Indiana University School of Medicine
  More Information

Additional Information:
Clinical Trial Flowcharts. Click "Bone Marrow & Stem Cell Transplant"  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00670423     History of Changes
Other Study ID Numbers: 0803-17; IUCRO-0204
Study First Received: April 29, 2008
Last Updated: July 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
Tacrolimus
Sirolimus
Bortezomib
Acute Graft Versus Host Disease
Allogeneic Peripheral Blood Stem Cell Transplantation

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Sirolimus
Everolimus
Tacrolimus
Bortezomib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
 Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013