Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors

May 23, 2017 updated by: John Koreth, MD, Dana-Farber Cancer Institute

Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study

A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.

In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.

You will receive 3 drugs for your GVHD prophylaxis:

Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.

Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.

Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
  • HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
  • ECOG performance status 0-2
  • Adequate organ function
  • Able to understand and willing to sign a written informed consent document
  • Agrees to practice adequate contraception per study requirements

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Recipient of prior allogeneic or autologous stem cell transplantation
  • Prior abdominal radiation therapy
  • HIV-positive on combination antiretroviral therapy
  • Seropositive for hepatitis B or C
  • Allergies to bortezomib, boron, or mannitol
  • Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
  • Uncontrolled bacterial, viral or fungal infections
  • Seizures or history of seizures
  • History of another non-hematologic malignancy unless disease-free for at least 5 years
  • Uncontrolled intercurrent illness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Velcade/Tac/MTX

Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV

Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid

Drug: Methotrexate. Methotrexate 15 mg/m^2 IV
Drug: Bortezomib
Bortezomib 1.3 mg/m^2 IV
Other Names:
  • Velcade
Drug: Tacrolimus
Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate
Methotrexate 15 mg/m^2 IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
Time Frame: Day 100
The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
Day 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion
Time Frame: Day 30
To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) >/= 500 cells/u/L
Day 30
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion
Time Frame: 1 year
Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.
1 year
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

February 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

March 24, 2011

First Submitted That Met QC Criteria

March 24, 2011

First Posted (Estimate)

March 28, 2011

Study Record Updates

Last Update Posted (Actual)

May 30, 2017

Last Update Submitted That Met QC Criteria

May 23, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11-007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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