Chronic Graft-versus-host Disease
Conditions
Keywords
Steroid refractory chronic graft vs host disease (cGVHD), Bortezomib, Velcade
Brief summary
The purpose of this study is to see if bortezomib (Velcade) is effective in the treatment of refractory cGVHD.
Detailed description
Graft vs. host disease represents the most formidable problem following allogeneic hematopoietic stem cell transplantation for hematological diseases. Chronic graft-versus-host disease (cGVHD) is the most serious and common long-term complication of this treatment in patients surviving more than 100 days. Some patients are requiring immunosuppressive therapy for years. cGVHD is associated with a high degree of morbidity and mortality and remains a major cause of late death. When standard treatment with steroids is ineffective or poorly tolerated, effective therapeutic options are limited. Patients with uncontrolled cGVHD with initial therapy including systemic steroids respond poorly to second line options. Recent studies have demonstrated Bortezomib safety in the prophylaxis, and improvement of GVHD suggesting its efficacy.This study is done to evaluate the potential of bortezomib in treating refractory cGVHD.
Interventions
DRUGBortezomib
1.6 mg/m2 IV infusion on days 1, 8, 15, 22 of each 35 day cycle, for up to 6 cycles.Patients who continue to respond during the initial treatment phase with no ongoing significant adverse events will be eligible to receive up to 6 additional cycles.This maintenance dose will be administered on days 1 and 15.
Sponsors
Millennium Pharmaceuticals, Inc.
Baylor Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * ≥18 years old. * Able to understand and sign informed consent. * Diagnosis of steroid-refractory cGVHD is defined as either failure to improve after 2 months or progression after 1 month of standard steroid based therapy. * No previous treatment with Bortezomib for cGVHD * ECOG PS\<3 * Total Bilirubin ≤ 1.5x ULN * Life expectancy \> 3months. * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control for the duration of the study and through a minimum of 30 days after the last dose of bortezomib. * Male subject agrees to use an acceptable method for contraception for the duration of the study and through a minimum of 30 days after the last dose of study drug.
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effectiveness and safety of the proteasome inhibitor Bortezomib (Velcade) in the treatment of steroid refractory chronic Graft-vs-Host Disease (cGVHD) | 19 months | Total time frame including treatment and follow up is 19 months(Maximum of 6 cycles during initial treatment phase, 6 cycles in maintenance phase, and follow up phase for 6 months). Subjects will be assessed for signs and symptoms of cGVHD on day 1 of every cycle using standardized criteria for diagnosis of cGVHD, new clinical scoring system, and new guidelines for global assessment of chronic GVHD severity per NIH consensus development project on criteria for clinical trials in chronic GVHD. Safety will be assessed in terms of adverse events for 30 days following the last dose to a maximum of 6 months. Adverse events will be recorded through out the trial and will be followed by investigator until resolution. |
Secondary
| Measure | Time frame |
|---|---|
| To examine blood cells from patients who develop steroid resistant cGVHD following allogeneic HSCT for disease related gene signatures using DNA microarray analysis techniques | 12 months |
Countries
United States
Outcome results
None listed