Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation
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|ClinicalTrials.gov Identifier: NCT00369226|
Recruitment Status : Completed
First Posted : August 29, 2006
Results First Posted : July 25, 2013
Last Update Posted : July 25, 2013
|Condition or disease||Intervention/treatment||Phase|
|Hematologic Malignancies||Drug: Bortezomib (Velcade) Drug: Tacrolimus Drug: Methotrexate Procedure: blood stem cell transplantation||Phase 1 Phase 2|
- In this study we are looking for the highest dose of Velcade that can be given to people safely when given with tacrolimus and methotrexate. Not everyone who participates in the study will receive the same amount of the study drug. The dose the participant will receive depends upon the number of subjects enrolled on the study and how well they have tolerated their doses of the drug.
- Before Transplant: In addition to the chemotherapy drugs, fludarabine and busulfex, for the participants non-myeloablative transplant, they will also start taking tacrolimus orally three days before their transplant.
- After Transplant Medication: Methotrexate; Intravenously on days 1, 3, 6 & 11 after transplant for a total of 4 doses. Tacrolimus; Continue taking orally once daily. Velcade: Intravenously on days 1, 4 & 7 after transplant, a total of 3 doses. Filgrastim: Subcutaneous injection daily starting the day after transplant and continuing until the participant blood counts have recovered.
- After Transplant Physical Exams & Tests: Participants will have physical exams and blood tests every week for 1 month. After 1 month, a none marrow biopsy will be performed to look for evidence of the donor's cells in the participants bone marrow.
- Following the 1 month period of time, participants will be seen every few weeks. Another bone marrow biopsy, as well as blood tests, will be taken 3-4 months after the transplant to review the disease status. At this point, participants will come into the clinic about every 3 months, or as determined by their physician for about one year.
- While the study ends at 12 months after transplant, we would like to keep track of the participants medical condition for the rest of their life.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Bortezomib (Velcade) in Addition to Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation|
|Study Start Date :||August 2006|
|Actual Primary Completion Date :||July 2010|
|Actual Study Completion Date :||September 2011|
|Experimental: Bortezomib/Tacrolimus/Methotrexate post HSCT||
Drug: Bortezomib (Velcade)
Infusion for a total of 3 dosesDrug: Tacrolimus
Taken until Doctor determines it is not necessary any moreDrug: Methotrexate
Infusion for a total of 4 dosesProcedure: blood stem cell transplantation
Allogeneic Non-myeloablative peripheral blood stem cell transplantation
- The Maximally Tolerated Dose (MTD) of Bortezomib (Velcade) That Can be Administered With Tacrolimus and Methotrexate After Mismatched Allogeneic Non-myeloablative Peripheral Blood Stem Cell (PBSC) Transplantation [ Time Frame: by day 45 post PBSC infusion ]
The MTD of bortezomib was evaluated at 3 dose levels:
Dose level 1: 1.0 mg/m^2 Dose level 2: 1.3 mg/m^2 Dose level 3: 1.5 mg/m^2 Cohorts of 3-5 pts were enrolled at each dose level. At any dose level, if no DLT in the first 3, 4, or 5 pts, then dose escalation would occur.
If 3 evaluable pts in cohort, and 1 of 3 experiences DLT then 2 additional pts treated at the same dose level. If >=1 of 2 additional pts experience DLT then previous dose level will be MTD. If no DLT in additional 2 pts then dose escalation will occur. If 4 evaluable pts in cohort, and 1 of the 4 experiences DLT then 1 additional pt treated at same dose level. If this additional pt experiences DLT then the previous dose will be declared to be the MTD. If additional pt does not experience DLT, then dose escalation will take place. If 5 evaluable pts in cohort, and 1 experiences DLT, then dose escalation will take place. If >=2 of first 3, 4, or 5 pts experience DLT then the previous dose will be declared MTD.
- Successful Initial Engraftment by Day 45 Post Peripheral Blood Stem Cell (PBSC) Infusion and Administration of Bortezomib (Velcade), Tacrolimus and Methotrexate [ Time Frame: by day 45 post PBSC infusion ]Percentage of participants who did not experience failure to engraft or relapse or death before assessment.
- Incidence of Grade II-IV Acute Graft Versus Host Disease (GVHD) by Day 100. [ Time Frame: by day 100 after peripheral blood stem cell (PBSC) infusion ]
- Sustained Engraftment Following Transplant. [ Time Frame: by day 100 post transplant ]As measured by median total donor chimerism at day 100.
- Incidence of Chronic Graft Versus Host Disease (Chronic GVHD). [ Time Frame: by 1 year after PBSC infusion ]Number of participants with chronic GVHD at 1 year post transplant.
- Overall Survival and Progression-free Survival. [ Time Frame: by 1 year after PBSC infusion ]Progression is defined as disease relapse or disease progression since transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00369226
|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||John Koreth, MD||Dana-Farber Cance Institute|