Bortezomib Plus Tacrolimus and Methotrexate to Prevent GVHD After Mismatched Allogeneic Non-Myeloablative Blood Stem Cell Transplantation
This study has been completed.
Sponsor:
Dana-Farber Cancer Institute
Collaborators:
Brigham and Women's Hospital
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
John Koreth, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00369226
First received: August 24, 2006
Last updated: February 16, 2012
Last verified: February 2012
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Purpose
The purpose of this study is to determine if Velcade (also known as bortezomib) can help prevent graft versus host disease (GVHD) developing after transplantation. This is done by using a combination of three immune suppressive medications: Velcade, tacrolimus and methotrexate. Stem cell transplantation is one of the options for patients with cancer of the blood or blood forming organs. Recently, allogeneic stem cell transplants have been performed using lower doses of chemotherapy and radiotherapy: non-myeloablative or "mini" transplants. GVHD is a significant problem that may occur even after "mini" transplantations. Information from other research studies, suggests that Velcade may help to reduce the risk of developing GVHD when given early after transplantation.
| Condition | Intervention | Phase |
|---|---|---|
|
Hematologic Malignancies |
Drug: Bortezomib (Velcade) Drug: Tacrolimus Drug: Methotrexate Procedure: blood stem cell transplantation |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | 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 |
Resource links provided by NLM:
Further study details as provided by Dana-Farber Cancer Institute:
Primary Outcome Measures:
- 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 [ Time Frame: by day 45 post PBSC infusion ] [ Designated as safety issue: Yes ]
- to determine the successful initial engraftment rate by day 45 post PBSC infusion and administration of Velcade, tacrolimus and methotrexate [ Time Frame: by day 45 post PBSC infusion ] [ Designated as safety issue: No ]
- to determine the incidence of grade II-IV acute GVHD by day 100 in this patient population. [ Time Frame: by day 100 after administration of VELCADE with Tacrolimus and Methotrexate ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- To assess sustained engraftment following PBSC transplantation [ Time Frame: by day 100 post transplant ] [ Designated as safety issue: No ]
- to determine the incidence of extensive GVHD after MTD Velcade by 1 year after PBSC infusion [ Time Frame: by 1 year after PBSC infusion ] [ Designated as safety issue: Yes ]
- to determine overall and progression-free survival of this patient population. [ Time Frame: by 1 year after PBSC infusion ] [ Designated as safety issue: No ]
| Enrollment: | 45 |
| Study Start Date: | August 2006 |
| Study Completion Date: | September 2011 |
| Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: Bortezomib (Velcade)
Infusion for a total of 3 doses
Drug: Tacrolimus
Taken until Doctor determines it is not necessary any more
Drug: Methotrexate
Infusion for a total of 4 doses
Procedure: blood stem cell transplantation
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369226
Locations
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | |
| Boston, Massachusetts, United States, 02115 | |
| Brigham and Women's Hospital | |
| Boston, Massachusetts, United States, 02115 | |
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Millennium Pharmaceuticals, Inc.
Investigators
| Principal Investigator: | John Koreth, MD | Dana-Farber Cance Institute |
More Information
No publications provided by Dana-Farber Cancer Institute
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | John Koreth, MD, Principal Investigator, Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00369226 History of Changes |
| Other Study ID Numbers: | 06-065, X05175 |
| Study First Received: | August 24, 2006 |
| Last Updated: | February 16, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Dana-Farber Cancer Institute:
|
Velcade Bortezomib Allogeneic Stem Cell Transplant GVHD |
Additional relevant MeSH terms:
|
Neoplasms Graft vs Host Disease Hematologic Neoplasms Immune System Diseases Neoplasms by Site Hematologic Diseases Methotrexate Bortezomib Tacrolimus Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Pharmacologic Actions |
Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Protease Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013