Bortezomib in Patients With Chronic Graft Versus Host Disease
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study Of Weekly Subcutaneous Bortezomib In Patients With Steroid-Refractory Or -Dependent Chronic Graft Versus Host Disease|
- Safety of weekly bortezomib in patients with chronic graft versus host disease panobinostat in combination with cisplatin and pemetrexed [ Time Frame: Up to 9 months ] [ Designated as safety issue: Yes ]Safety assessments will consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology, blood chemistry, regular measurement of vital signs and the performance of physical examination. Safety will be assessed according to the NCI CTCAE v4.
- cGVHD Response [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]Specific events of interest are recurrence of GVHD and relapse of primary cancer as measured by clinical cGVHD staging system based upon specific signs, degree of organ involvement (mild, moderate, severe), laboratory data, and/or histopathological confirmation.
- Role of bortezomib on induction of immune tolerance by performing correlative studies [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]Seven -10 mL of whole blood will be collected at each timepoint.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Bortezomib starting dose is 0.2 mg/m2 subcutaneously which will be given weekly with incremental increase of 0.2 mg/m2 every other week, if no improvement is seen, and no dose limiting toxicities are observed to the maximum dose of 1.6 mg/m2. Bortezomib will be administered in the outpatient clinic.
If improvements are seen at any dose level and patients have no DLTs, they will stay at their dose level until the end of the study. This is to avoid any possible toxicity while the patient is benefiting from their current dosing of bortezomib. If the continuous improvement in GVHD stalls at any point, or the GVHD progresses after the original improvement, while the dose level is maintained, then the dose will be increased to the next dose level. Patients will remain enrolled until exacerbation of the GVHD on increasing dose schedule or closure of the study. Clinical activity will be monitored every other week after the initiation of bortezomib until the study closes.
Other Name: Velcade
Bone marrow transplantation offers great promise for the treatment of a variety of diseases, particularly hematological malignancies. The incidence of acute GVHD has significantly decreased due to significant improvements in human leukocyte antigen (HLA) matching of the donors and recipients, more efficient GVHD prophylaxis regimens and the use of reduced-intensity preparative regimen. However, cGVHD remains a significant cause for increased morbidity and mortality associated with allogeneic stem cell transplantation.
While many of the patients with cGVHD respond initially to higher doses of steroids, cGVHD usually relapses during or following steroid taper. Because of the significant impact of steroids on this patient population, there is an urgent need for medications to take the place of high dose steroid use in this patient population.
We hypothesize that bortezomib can modulate the immune system and can be used to treat GVHD. At the same time bortezomib post transplant can induce a graft versus leukemia or lymphoma effect. Bortezomib has been used with minimal toxicity in post transplant setting for patients with aggressive multiple myeloma and also for acute graft versus host disease.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01672229
|United States, California|
|University of California Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|Principal Investigator:||Mehrdad Abedi, MD||University of California, Davis|