Bortezomib and Reduced Intensity Allogenic Stem Cell Transplantation for Lymphoid Malignancies
This trial is active, not recruiting.
|Treatments||carmustine, cytarabine, etoposide, melphalan, rituximab, bortezomib, allogeneic stem cell infusion|
|Sponsor||M.D. Anderson Cancer Center|
|Collaborator||Millennium Pharmaceuticals, Inc.|
|Start date||February 2007|
|End date||February 2017|
|Trial size||52 participants|
|Trial identifier||NCT00439556, 2006-0066, NCI-2010-00579|
The goal of this clinical research study is to find the highest tolerable dose of Velcade (bortezomib) that can be given with BEAM (carmustine, etoposide, cytarabine and melphalan) and rituximab in patients with lymphoma who receive a stem cell transplant.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Maximum tolerated dose (MTD) of Bortezomib
time frame: 90 days after the start of treatment
Incidence of Graft-Versus-Host Disease (GVHD)
time frame: 90 days
Male or female participants up to 70 years old.
Inclusion Criteria: 1. Up to 70 years of age. 2. Any histological subtype of CD20+ lymphoid malignancies or T-cell lymphoid malignancies. 3. Patients with CD20+ lymphoid malignancies in relapse after failing >/= 1 prior regimen of conventional treatment and not eligible for non-myeloablative transplant. Patients with T-Cell lymphoid malignancies can either be in relapse or newly diagnosed with high risk features (such as high IPI of >/= 2). 4. Patients with prior non-myeloablative transplant are eligible if not from the same donor. 5. A fully-matched or one-antigen mismatched sibling or unrelated donor. 6. Left ventricular EF >/= 40% with no uncontrolled arrythmias or symptomatic heart disease.. 7. FEV1, FVC and DLCO >/= 40%. 8. Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3X upper limit of normal, 9. SGPT < 3X upper limit of normal. 10. Voluntary signed, written IRB-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 11. Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study. Exclusion Criteria: 1. Past history of anaphylaxis following exposure to rituximab or VELCADE®, boron or mannitol 2. History of grade 3 or 4 NCI toxicity with prior VELCADE® therapy 3. Patient with active CNS disease. 4. Pregnant (Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 5. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C. 6. Patients with other malignancies diagnosed within 2 years prior to Study Day -13 (except skin squamous or basal cell carcinoma). 7. Active uncontrolled bacterial, viral or fungal infections. 8. Major surgical procedure or significant traumatic injury within 4 weeks prior to Day -13. 9. Serious, non-healing wound, ulcer, or bone fracture. 10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to Day -13. 11. History of Stroke within 6 months. 12. Myocardial infarction within the past 6 months prior to Study Day 1, or has New York Heart Association (NYHA) Class III or IV heart failure or arrythmia, unstable angina, uncontrolled congestive heart failure or arrythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.Prior to study entry, any ECG abnormality at screening must be documented by investigator as not medically relevant. 13. Uncontrolled hypertension(>/=140/90) . 14. Uncontrolled chronic diarrhea. 15. A prior allogeneic transplant from the same donor. 16. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 17. Patient has received other investigational drugs within 3 weeks before enrollment. 18. Active peripheral neuropathy greater or equal to grade 2.
|Official title||Bortezomib (Velcade) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies|
|Principal investigator||Issa F. Khouri, MD|
|Description||Carmustine, etoposide, cytarabine, and melphalan are designed to kill lymphoma cells by inserting into the cell DNA. Rituximab is a monoclonal antibody that targets a specific marker on the surface of lymphoma cells and causes it to die. Bortezomib works by blocking proteasomes, which are clusters of proteins necessary for cancer cell growth. Cancer cells may be sensitive to drugs like bortezomib because tumor cells have more proteins than normal cells. Bortezomib enters the tumor cells and affects the way they divide. When cancer cells cannot divide, they die. If you are found to be eligible to take part in this study, you will receive carmustine through a needle in your vein over 1 hour on Day 1. On Days 2-5 you will be given cytarabine by vein over 1 hour and etoposide by vein over 3 hours. This will be repeated every 12 hours on Days 2-5. On Day 6 you will be given melphalan by vein over 30 minutes. On Day 7 the stem cells that were collected earlier from a donor will be given back to you ("transplanted") through your catheter over 30-45 minutes. You will also receive rituximab by vein, over 5 to 7 hours before the transplant and then weekly, for a total of 4 doses. In addition, if you are receiving a matched unrelated or mismatched donor transplant, on days 5-6 you will also be given thymoglobulin by vein over 4-6 hours. Patients with T-cell lymphoma will not receive Rituxan. Bortezomib will be given by vein over 1 minute 13 days, 6 days, and 1 day before the transplant, and again 2 days after the transplant. G-CSF will be injected under the skin once a day until the your blood counts return to a normal level, starting 7 days after the transplant. Sometimes the infused donor cells cause inflammation of the skin, liver, and gut, and a reaction called graft-versus-host disease (GVHD) occurs. To prevent GVHD, tacrolimus will be given by vein non-stop starting 2 days before the transplant. It will be changed to oral tablets before you leave the hospital. You will take tacrolimus for about 6-8 months after the transplant. Methotrexate will be given for the same purpose on Days 1, 3, and 6 after the transplant by vein over a few minutes. Patients receiving a matched unrelated or mismatched donor will also be given methotrexate on day 11 after the transplant. You will be required to stay in the hospital from about 2 weeks before the transplant until about 2-3 weeks after the transplant. You must stay in the Houston area for about 100 days after the transplant. During the first 100 days after transplantation, blood (about 6 teaspoons) will be drawn for routine tests. Blood (about 20-30 teaspoons) will also be drawn daily while you are in the hospital to check the effect of the transplant. You will receive transfusions of blood and platelets as needed. You will have a bone marrow biopsy/aspirate and/or chest x-ray if your doctor thinks it is necessary. Beginning 1 month after transplantation, then every 3 months for 1 year, and then every 6 months for 5 years, you will have CT scans, positron emission tomography (PET) or Gallium scans (a nuclear medicine test that uses a special camera to take pictures of special tissues), and a bone marrow biopsy/aspirate. These tests will be done to check the status of the disease. You will be on active study for 5 years after the transplant. You will be taken off study if the disease gets worse or intolerable side effects occur. You should talk to the study doctor if you want to leave the study early. If you are taken off study early, you still may need to return for routine post-transplant follow-up visits, if your transplant doctor decides it is needed. It may be life-threatening to leave the study early during the conditioning regimen without following up with the stem cell transplant, because your blood cell counts may be dangerously low. This is an investigational study. Bortezomib and rituximab are FDA approved and commercially available. Their use in this study, however, is investigational since it is used with transplantation. All other chemotherapy drugs are FDA approved and commercially available. Up to 52 patients will take part in this study. All will be enrolled at MD Anderson.|
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