Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.
In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.
|Leukemia Lymphoma Myelodysplastic Syndrome||Drug: Bortezomib Drug: Tacrolimus Drug: Methotrexate||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study|
- The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion [ Time Frame: Day 100 ]The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
- The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion [ Time Frame: Day 30 ]To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) >/= 500 cells/u/L
- The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion [ Time Frame: 1 year ]Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.
- The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion [ Time Frame: 1 year ]
|Study Start Date:||May 2011|
|Study Completion Date:||November 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV
Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate. Methotrexate 15 mg/m^2 IV
Bortezomib 1.3 mg/m^2 IV
Other Name: VelcadeDrug: Tacrolimus
Tacrolimus 0.05 mg/kg PO bidDrug: Methotrexate
Methotrexate 15 mg/m^2 IV
Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.
You will receive 3 drugs for your GVHD prophylaxis:
Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.
Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.
Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01323920
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||John Koreth, MBBS, DPhil||Dana-Farber Cancer Institute|