- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00369226
Bortezomib Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease (GVHD) After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
- 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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with hematologic malignancies including myelodysplastic syndrome (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
- Aspartate aminotransferase (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, chronic myeloid leukemia)
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bortezomib/Tacrolimus/Methotrexate post HSCT
|
Infusion for a total of 3 doses
Taken until Doctor determines it is not necessary any more
Infusion for a total of 4 doses
Allogeneic Non-myeloablative peripheral blood stem cell transplantation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
by day 45 post PBSC infusion
|
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.
|
by day 45 post PBSC infusion
|
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
|
by day 100 after peripheral blood stem cell (PBSC) infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Sustained Engraftment Following Transplant.
Time Frame: by day 100 post transplant
|
As measured by median total donor chimerism at day 100.
|
by day 100 post transplant
|
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.
|
by 1 year after PBSC infusion
|
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.
|
by 1 year after PBSC infusion
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John Koreth, MD, Dana-Farber Cance Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms
- Neoplasms by Site
- Hematologic Diseases
- Hematologic Neoplasms
- Graft vs Host Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Calcineurin Inhibitors
- Bortezomib
- Methotrexate
- Tacrolimus
Other Study ID Numbers
- 06-065
- X05175
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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