Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease

June 29, 2015 updated by: John Koreth, MD, Dana-Farber Cancer Institute

A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease

The purpose of this research study is to determine the effectiveness of bortezomib (Velcade) plus prednisone for treating chronic graft versus host disease (cGVHD) and the safety of this drug combination in this patient population. Chronic GVHD is a medical condition that may occur after allogeneic stem cell transplantation. The donor's immune system may recognize the participants body (the host) as foreign and attempt to "reject" it. Bortezomib has been used in other research studies, and information from those studies suggests that this drug may help to control the abnormal immune responses that underlie cGVHD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  • Each treatment cycle lasts five weeks, during which time participants will come to the clinic to receive bortezomib intravenously once a week for the first 4 weeks. Prednisone will be taken orally on a daily basis and dose reduction may be initiated after 1 cycle of therapy.
  • During all treatment cycles, participants will have the following: physical exam and blood work. At the end of cycle 3 (week 15) the participants cGVHD will be evaluated. These assessments may include an eye examination, a skin examination, a pulmonary function test and/or, a flexion assessment test.
  • Participants will receive 3 cycles of bortezomib.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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, 02115
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens
  • 100 days or more past stem cell transplantation
  • Recipients of matched or mismatched, related or unrelated adult donor stem cells
  • Must have cGVHD requiring systemic therapy
  • No addition or subtraction of other immunosuppressive medications. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug. However, if cGVHD occurs during a taper of immune suppression, the medication(s) may not be increased back up to therapeutic level, but will continue a the taper dose for the 15 week study duration
  • Adequate bone marrow, hepatic and renal function as outlined in the protocol
  • Does not require hemodialysis
  • 18 years of age or older
  • ECOG Performance Status of 0-2 or Karnofsky performance score of 70% or greater
  • Life expectancy of more than 3 months

Exclusion Criteria:

  • Systemic steroid therapy in the 4 weeks prior to enrollment
  • Active malignant disease after transplantation. Complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy will not be considered in this category
  • Active uncontrolled infection
  • Peripheral neuropathy CTC Grade 1 (or greater) with pain in the 4 weeks before enrollment. Other neurological deficits must be reviewed with the study PI prior to study entry
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Hypersensitivity to bortezomib, boron, or mannitol
  • Female subject is pregnant or breast-feeding
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Velcade (bortezomib)
Drug: bortezomib
Given intravenously at a dose of 1.3 mg/m^2 once a week for the first four weeks of a five week cycle for a total of 3 cycles
Other Names:
  • Velcade
Drug: Prednisone
Taken orally once a day at a dose of 0.5-1 mg/kg. Dose reduction may be initiated after 1 cycle of therapy. A suggested taper is 10-25% every 1-2 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Time Frame: Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy

Participants had their cGVHD evaluated per NIH consensus criteria:

Complete response: resolution of all reversible manifestations of cGVHD.

Partial response: a decrease ≥ 1 point on a 3-point organ-specific scale or 2 points or more on a 10-point global scale without progression in any organ sites.

Stable disease: no evidence of cGVHD response without evidence of progressive cGVHD.

Progressive cGVHD: increase of ≥ 1 point on an organ-specific 3-point scale, addition of a new immunosuppressive agent prior to the completion of 15 weeks of combination therapy, or requirement an increase in the total daily dose of corticosteroids above a participant's baseline corticosteroid dose during the 15-week combined treatment period.

Mixed response: a response in primary sites of cGVHD involvement but interval progressive cGVHD in other organs or sites.

Responses were not scored for oral or ocular cGVHD, since topical therapies were permitted during the study.
Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Time Frame: After 15 weeks of bortezomib plus prednisone therapy
The participants' total daily steroid dose was recorded at baseline and after a 15 week course of treatment. Starting at a dose of 0.5-1 mg/kg, dose reduction of steroids was permitted after 1 cycle of therapy. The suggested taper was 10-25% every 1-2 weeks. .
After 15 weeks of bortezomib plus prednisone therapy
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Time Frame: Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn
Participants' toxicities were graded based on the CTCAE version 3.0. The toxicities were then given an attribution to the velcade treatment: unrelated, unlikely, possible, probable, definite.
Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy
Time Frame: 1 year after the start of study treatment
Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.
1 year after the start of study treatment
Overall and cGVHD Progression-free Survival by 1 Year After Therapy
Time Frame: 2 years
2 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dana-Farber Cancer Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Millennium Pharmaceuticals, Inc.

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 30, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 31, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 08-191

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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