Phase I/II Trial of Bortezomib (Velcade) in Addition to Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease After Mismatched Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation
18 Years
N/A
Both
Hematologic Malignancies
Trial Information
Phase I/II Trial of Bortezomib (Velcade) in Addition to Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease After Mismatched Allogeneic Non-Myeloablative Peripheral Blood Stem Cell Transplantation
- 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.
Inclusion Criteria:
- Patients with hematologic malignancies including MDS, who are at a high risk of
complications after myeloablative transplantation
- Patients have a donor (both related and unrelated) who are mismatched according to
protocol criteria
- 18 years of age or older
- Performance status 0-2
- Life expectancy of > 100 days
- Female subject is either post-menopausal or sterilized or willing to use an
acceptable form of birth control
- Male subject agrees to use an acceptable form of birth control
Exclusion Criteria:
- Evidence of HIV infection
- Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction
- AST > 90
- Known active hepatitis B or C
- Serum creatinine > 2.0
- Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment
- Prior allogeneic stem cell transplant
- Patients with myeloproliferative disease (e.g. myelofibrosis, essential
thrombocythemia, polycythemia vera, CML)
- Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV
hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities
- Hypersensitivity to Velcade, boron or mannitol
- Pregnant or breast feeding
- Patient has received other investigational drugs 14 days before enrollment
- Serious medical or psychiatric illness
- Another active solid tumor malignancy at the time of study entry
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Outcome Measure:
To establish the maximally tolerated dose of Velcade that can be administered with Tacrolimus and Methotrexate after mismatched allogeneic non-myeloablative peripheral blood stem cell (PBSC) transplantation
Outcome Time Frame:
by day 45 post PBSC infusion
Safety Issue:
Yes
Principal Investigator
John Koreth, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cance Institute
Authority:
United States: Institutional Review Board
Study ID:
06-065
NCT ID:
NCT00369226
Start Date:
August 2006
Completion Date:
September 2011
Related Keywords:
- Hematologic Malignancies
- Velcade
- Bortezomib
- Allogeneic Stem Cell Transplant
- GVHD
- Neoplasms
- Graft vs Host Disease
- Hematologic Neoplasms
Name | Location |
|---|---|
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Brigham and Women's Hospital | Boston, Massachusetts 02115 |
