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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


Phase 1
18 Years
79 Years
Open (Enrolling)
Both
Mantle Cell Lymphoma, Lymphoma

Thank you

Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Time Frame:

Continual reassessment for toxicity with each 21 day cycle

Safety Issue:

Yes

Principal Investigator

Jorge Romaguera, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2006-0697

NCT ID:

NCT00477412

Start Date:

April 2007

Completion Date:

Related Keywords:

  • Mantle Cell Lymphoma
  • Lymphoma
  • Mantle Cell Lymphoma
  • Lymphoma
  • Bortezomib
  • LDP-341
  • MLN341
  • Velcade
  • Cyclophosphamide
  • Neosar
  • Cytoxan
  • Doxorubicin
  • Adriamycin
  • Rubex
  • Rituximab
  • Vincristine
  • Methotrexate
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Mesna
  • Dexamethasone
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

Hackensack University Medical CenterHackensack, New Jersey  07601
UT MD Anderson Cancer CenterHouston, Texas  77030