Bortezomib 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.
Chronic Graft Versus Host Disease
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Bortezomib (Velcade) Plus Prednisone for Initial Therapy of Chronic Graft Versus Host Disease|
- 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 ] [ Designated as safety issue: No ]
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.
- 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 ] [ Designated as safety issue: No ]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 [ Time Frame: Toxicities were collected from the start of treatment through 15 weeks of therapy or end of study treatmetn ] [ Designated as safety issue: Yes ]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 [ Time Frame: 1 year after the start of study treatment ] [ Designated as safety issue: No ]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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
|Experimental: Velcade (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 Name: VelcadeDrug: 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00815919
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||John Koreth, MBBS, DPhil||Dana-Farber Cancer Institute|