Bortezomib (Velcade) Plus Rituximab-HyperCVAD in Patients With Mantle Cell Lymphoma
Overview[ - collapse ][ - ]
Purpose | The goal of this clinical research study is to learn if bortezomib (in combination with rituximab plus 2 different intensive chemotherapy regimens) can help to control the disease in patients with mantle cell lymphoma. The safety of these drug combinations will also be studied. |
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Condition | Mantle Cell Lymphoma Lymphoma |
Intervention | Drug: Bortezomib Drug: Rituximab Drug: Cyclophosphamide Drug: Vincristine Drug: Methotrexate Drug: Cytarabine Drug: Doxorubicin |
Phase | Phase 1 |
Sponsor | M.D. Anderson Cancer Center |
Responsible Party | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier | NCT00477412 |
First Received | May 21, 2007 |
Last Updated | March 14, 2014 |
Last verified | March 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | May 21, 2007 |
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Last Updated Date | March 14, 2014 |
Start Date | April 2007 |
Estimated Primary Completion Date | Not Provided |
Current Primary Outcome Measures | Maximum Tolerated Dose (MTD) [Time Frame: Continual reassessment for toxicity with each 21 day cycle] [Designated as safety issue: Yes] |
Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
Brief Title | Bortezomib (Velcade) Plus Rituximab-HyperCVAD in Patients With Mantle Cell Lymphoma |
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Official Title | Phase I Study of Bortezomib (Velcade) Plus Rituximab-HyperCVAD Alternating With Bortezomib Plus Rituximab-High Dose Methotrexate/Cytarabine in Patients With Untreated Aggressive Mantle Cell Lymphoma |
Brief Summary | The goal of this clinical research study is to learn if bortezomib (in combination with rituximab plus 2 different intensive chemotherapy regimens) can help to control the disease in patients with mantle cell lymphoma. The safety of these drug combinations will also be studied. |
Detailed Description | You will receive 2 different drug combinations on this study. The first combination will consist of bortezomib and rituximab given together with an intensive chemotherapy regimen (cyclophosphamide, mesna, doxorubicin, vincristine, and dexamethasone). The second combination will consist of bortezomib and rituximab given together with another intensive chemotherapy regimen (methotrexate and Ara-C [cytarabine]). If you are found to be eligible to take part in this study, the first combination will be given during Cycles 1, 3, 5, and, if needed, Cycle 7. The first combination can be given on an outpatient basis (with no overnight hospital stay required), if your doctor allows it. The second combination will be given during Cycles 2, 4, 6, and, if needed, Cycle 8. It is recommended that the second combination be given on an inpatient basis so that study staff can monitor the effect of the study drugs, for your safety. You will have a central venous catheter (CVC) placed so that the chemotherapy can be given to you more easily. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. First combination: For the first combination (during each cycle), you will receive rituximab by vein over 6 hours on Day 1. Cyclophosphamide will be given by vein (over 3 hours each time) twice a day on Days 2-4. Mesna will be given continuously by vein on Days 2-4. Doxorubicin will be given over 15-30 minutes on Day 5. Vincristine will be given by vein over 15-30 minutes on Days 5 and 12. Dexamethasone will be given by mouth or by vein on Days 2-5 and Days 12-15. Bortezomib will be given over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on Day 5. Other drugs will be given before, during, and after chemotherapy to help prevent or decrease side effects, such as nausea and vomiting. These drugs will include Zofran® (ondansetron hydrochloride) given by vein over 15-30 minutes. Ciprofloxacin hydrochloride given by mouth twice a day for 10 days, Valtrex (valacyclovir) given by mouth for 10 days, and fluconazole given by mouth every day for 10 days. Ciprofloxacin hydrochloride, valacyclovir, and fluconazole will be given on the same days. This first combination will be alternated every 21 days with a second combination of bortezomib and rituximab plus an intensive chemotherapy regimen. To help prevent infections, you will receive Filgrastim (G-CSF) injections just under your skin, starting at 24-36 hours after the end of the doxorubicin infusion, once a day until your white blood cells recover. Second combination: For the second combination (during each cycle), you will receive rituximab by vein over 6 hours on Day 1. Methotrexate will be given by vein over 24 hours on Day 2. Cytarabine will be given by vein (over 2 hours each time) every 12 hours on Days 3-4. Other drugs will be given before, during, and after chemotherapy to help prevent or decrease side effects, such as nausea and vomiting. These drugs will include Zofran® (ondansetron hydrochloride) given by vein over 15-30 minutes. Ciprofloxacin hydrochloride given by mouth twice a day for 10 days, Valtrex (valacyclovir) given by mouth for 10 days, and fluconazole given by mouth daily for 10 days. Ciprofloxacin hydrochloride, valacyclovir, and fluconazole will be given on the same days. When you receive methotrexate, you will also be given leucovorin by mouth to help prevent side effects. Blood (about 1 tablespoon) will be drawn 24 and 48 hours after the end of the methotrexate infusion so that the study doctor can learn when it is best to stop giving you leucovorin. To help prevent infections, you will receive Filgrastim (G-CSF) injections just under your skin, starting at 24-36 hours after the end of the doxorubicin infusion, once a day until your white blood cells recover. During this study, blood (about 1 tablespoon) will be drawn 2-3 times a week for routine tests. After every 2 cycles, your tumor(s) will be measured using x-rays or CT scans. You will have a bone marrow biopsy/aspirate sample collected. If the study doctor thinks it is necessary, you may have a MUGA scan or an ECHO. You will have an exam of your colon (a colonoscopy). The colonoscopy will be performed before you receive Cycle 3 of the combination bortezomib with intensive chemotherapy, and (if necessary) before Cycle 7 of the combination bortezomib with intensive chemotherapy. Biopsy samples of the colon will be taken during this exam. To perform a colonoscopy, you will be given laxatives a day before and again right before the procedure. You will be given a sedative (to calm you) by vein followed by the insertion of a long tube into your rectum to the right side of your colon. You will be removed from this study if the disease gets worse or intolerable side effects occur. After receiving the study drugs, you will have follow-up visits at different time points. These visits will occur every 3 months for 1 year, then every 4 months for 2 years, then every 6 months for the next 2 years, and then once a year indefinitely. During these follow-up visits, you will have a complete physical exam, and blood (about 1 tablespoon) will be drawn for routine tests. You will have a chest x-ray, CT scans, and bone marrow and aspirate samples collected. This is an investigational study. All of the drugs used in this study are FDA approved and commercially available. Up to 110 patients will take part study. Up to 110 will be enrolled at MD Anderson. |
Study Type | Interventional |
Study Phase | Phase 1 |
Study Design | Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition |
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Intervention | Drug: Bortezomib 1st Combination = 1.3 mg/m^2 IV Push Over 3-5 Seconds Days 2 & 5; 2nd Combination = 0.7 mg/m^2 IV Push Days 1 & 6. Other Names:
375 mg/m^2 IV Over 6-8 Hours On Day 1 each cycle. Other Names: RituxanDrug: Cyclophosphamide 1st Combination = 300 mg/m^2 IV Over 3 Hours Twice Daily Days 2,3,& 4. Other Names: CytoxanDrug: Vincristine 1st Combination = 1.4 mg/m^2 (maximum 2 mg) IV Push Days 5 & 12. Drug: Methotrexate 2nd Combination = 200 mg/m^2 IV over 2 hours on Day 1, then 800 mg/m^2 IV over 22 hours on Day 2. Drug: Cytarabine 2nd Combination = 3g/m2 grams/m^2 IV over 2 Hours Twice a Day,On Days 3 & 4. Other Names:
Arm 1: 50 mg/m^2 IV Push Over 15-30 min on Day 5 Other Names:
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Study Arm (s) | Experimental: Bortezomib + Cyclophosphamide/Rituximab 1st Combination, Cycles 1,3,5 & 7 (if needed): Bortezomib + Rituximab + Cyclophosphamide + Doxorubicin + Vincristine; 2nd Combination, Cycles 2,4,6 & 8 (if needed): Rituximab + Methotrexate + Cytarabine. |
Recruitment Information[ + expand ][ + ]
Recruitment Status | Active, not recruiting |
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Estimated Enrollment | 110 |
Estimated Completion Date | Not Provided |
Estimated Primary Completion Date | April 2016 |
Eligibility Criteria | Inclusion Criteria: 1. Confirmed diagnosis of previously untreated nodular or diffuse mantle cell lymphoma and their blastoid cytologic variant. 2. ECOG Performance status of 0, 1, or 2. 3. Serum bilirubin <1.5mg/dl and serum creatinine < 2.0 mg/dl within 14 dyas before enrollment (unless higher levels are due to lymphoma) 4. Platelet count>100,000/mm^3 and absolute neutrophil count (ANC)>1,000/mm^3 within 14 days before enrollment (unless due to lymphoma). 5. Cardiac ejection fraction >/= 50% by ECHO or MUGA. 6. Age 18 years to 79 years. 7. Patients must be willing to receive transfusions of blood products. 8. Voluntary 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. 9. 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. 10. Male subject agrees to use an acceptable method for contraception for the duration of the study. Exclusion Criteria: 1. HIV infection. 2. CNS involvement. 3. Co-morbid medical or psychiatric illnesses that preclude treatment with intense dose chemotherapy. 4. Concurrent or previous malignancy with < 90% probability of survival at 5 years. 5. Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment. 6. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. 7. Patient has hypersensitivity to boron or mannitol. 8. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 9. Patient has received other investigational drugs within 14 days before enrollment. 10. Diagnosed or treated for another malignancy ,that has a less than 90% chance of survival at 5 years. 11. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. |
Gender | Both |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Not Provided |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT00477412 |
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Other Study ID Numbers | 2006-0697 |
Has Data Monitoring Committee | No |
Information Provided By | M.D. Anderson Cancer Center |
Study Sponsor | M.D. Anderson Cancer Center |
Collaborators | Millennium Pharmaceuticals, Inc. |
Investigators | Principal Investigator: Jorge Romaguera, MD M.D. Anderson Cancer Center |
Verification Date | March 2014 |
Locations[ + expand ][ + ]
Hackensack University Medical Center | Hackensack, New Jersey, United States, 07601 |
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UT MD Anderson Cancer Center | Houston, Texas, United States, 77030 |