Overview

This trial is active, not recruiting.

Conditions mantle cell lymphoma, lymphoma
Treatments bortezomib, rituximab, cyclophosphamide, vincristine, methotrexate, cytarabine, doxorubicin
Phase phase 1
Targets CD20, proteasome
Sponsor M.D. Anderson Cancer Center
Collaborator Millennium Pharmaceuticals, Inc.
Start date April 2007
End date April 2017
Trial size 110 participants
Trial identifier NCT00477412, 2006-0697, NCI-2010-00884

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
bortezomib Velcade
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.
rituximab Rituxan
375 mg/m^2 IV Over 6-8 Hours On Day 1 each cycle.
cyclophosphamide Cytoxan
1st Combination = 300 mg/m^2 IV Over 3 Hours Twice Daily Days 2,3,& 4.
vincristine
1st Combination = 1.4 mg/m^2 (maximum 2 mg) IV Push Days 5 & 12.
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.
cytarabine Ara-C
2nd Combination = 3g/m2 grams/m^2 IV over 2 Hours Twice a Day,On Days 3 & 4.
doxorubicin Adriamycin
Arm 1: 50 mg/m^2 IV Push Over 15-30 min on Day 5

Primary Outcomes

Measure
Maximum Tolerated Dose (MTD) of Bortezomib Added to Combination of Rituximab, Methotrexate, and Cytarabine Alternating with Bortezomib, Rituximab-HyperCVAD
time frame: Continual reassessment for toxicity with each 21 day cycle, up to 1 year

Secondary Outcomes

Measure
Median Time to Failure (TTF)
time frame: Up to 10 years

Eligibility Criteria

Male or female participants from 18 years up to 79 years old.

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 for at least 1 year before the Screening visit or surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of birth control, at the same time (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the time of signing the informed consent through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse. 10. Male subject, even if surgically sterilized (ie, status post vasectomy) agrees to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse. 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 bortezomib, 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. Participating in clinical trials with other investigational agents not included in this trial within 14 days of the start of this trial and throughout the duration of this trial. 10. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Additional Information

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
Principal investigator Michael Wang, MD, MS
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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by M.D. Anderson Cancer Center.