Bortezomib (Velcade) Plus Rituximab-HyperCVAD in Patients With Mantle Cell Lymphoma
Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Mantle Cell Lymphoma; Lymphoma
Intervention: Bortezomib (Drug); Rituximab (Drug); Cyclophosphamide (Drug); Vincristine (Drug); Methotrexate (Drug); Cytarabine (Drug); Doxorubicin (Drug)
Phase: Phase 1
Status: Active, not recruiting
Sponsored by: M.D. Anderson Cancer Center Official(s) and/or principal investigator(s): Michael Wang, MD, MS, Principal Investigator, Affiliation: M.D. Anderson Cancer Center
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.
Clinical Details
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
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Maximum Tolerated Dose (MTD) of Bortezomib Added to Combination of Rituximab, Methotrexate, and Cytarabine Alternating with Bortezomib, Rituximab-HyperCVAD
Secondary outcome: Time to Failure (TTF)
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 ZofranĀ® (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 ZofranĀ® (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.
Eligibility
Minimum age: 18 Years.
Maximum age: 79 Years.
Gender(s): Both.
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 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.
Locations and Contacts
Hackensack University Medical Center, Hackensack, New Jersey 07601, United States
University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States
Additional Information
University of Texas MD Anderson Cancer Center Website
Starting date: April 2007
Last updated: August 13, 2015
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