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

Primary Purpose

Chronic Graft Versus Host Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
Prednisone
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Graft Versus Host Disease focused on measuring cGVHD, Velcade, bortezomib

Eligibility Criteria

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

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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Velcade (bortezomib)

Arm Description

Outcomes

Primary Outcome Measures

Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
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.

Secondary Outcome Measures

Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
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. .
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
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.
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy
Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.
Overall and cGVHD Progression-free Survival by 1 Year After Therapy

Full Information

First Posted
December 30, 2008
Last Updated
June 29, 2015
Sponsor
Dana-Farber Cancer Institute
Collaborators
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00815919
Brief Title
Bortezomib Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
Official Title
A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Graft Versus Host Disease
Keywords
cGVHD, Velcade, bortezomib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Velcade (bortezomib)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response Rate After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Description
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.
Time Frame
Patients had their cGVHD assessed at Baseline and at 15 weeks or end of therapy
Secondary Outcome Measure Information:
Title
Proportion of Patients Tolerating >50% Steroid Dose Reduction After a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Description
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. .
Time Frame
After 15 weeks of bortezomib plus prednisone therapy
Title
The Toxicity of a 15 Week Course of Bortezomib Plus Prednisone in Patients With cGVHD
Description
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.
Time Frame
Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn
Title
Proportion of cGVHD Patients Requiring Prednisone by 1 Year After Therapy
Description
Participants who were still being followed 1 year after the start of therapy had their prednisone dose recorded.
Time Frame
1 year after the start of study treatment
Title
Overall and cGVHD Progression-free Survival by 1 Year After Therapy
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Koreth, MBBS, DPhil
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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

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