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Phase II Study of Bortezomib in Combination With Cyclophosphamide and Rituximab for Relapsed/Refractory Mantle Cell Lymphoma


Phase 2
18 Years
85 Years
Open (Enrolling)
Both
Mantle Cell Lymphoma, Lymphoma

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Trial Information

Phase II Study of Bortezomib in Combination With Cyclophosphamide and Rituximab for Relapsed/Refractory Mantle Cell Lymphoma


The Study Drugs:

Bortezomib is designed to block a protein that plays a role in cell function and growth.
This may cause cancer cells to die.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
slow or stop their growth and spread throughout the body. This may cause the cancer cells
to die.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive all of the
study drugs preferably through a central venous catheter (CVC) that will be left in place
the entire time that you are receiving the study drugs. A CVC is a sterile flexible tube
that will be placed into a large vein while you are under local anesthesia. You will sign a
separate consent form for this procedure, which will describe the procedure and the risk in
more detail.

You will receive rituximab by vein over 6 hours on Day 1 of every 21-day study cycle.

You will receive bortezomib by vein over 3 to 5 seconds, after you have received rituximab
on Day 1 of every cycle. You will also receive bortezomib on Days 4, 8, and 11 of every
cycle.

You will receive cyclophosphamide by vein over 3 hours 2 times each day (6 hours total each
day) on Days 2, 3, and 4 of every cycle. On these days, you will also receive mesna by vein
non-stop. Mesna is a drug that protects the bladder from damage by chemotherapy drugs. It
is used to decrease the risk of bleeding in the bladder.

You will receive G-CSF (filgrastim - a drug that is used to help build your white blood cell
counts and prevent infections) as an injection under the skin starting 24-36 hours after you
receive bortezomib. You will receive filgrastim 1 time each day until your white blood cell
counts recover.

Study Visits:

At each study visit, you will be asked about how you are feeling and about any other drugs
that you may be taking.

Throughout the study, blood (about 1 tablespoon each time) will be drawn 2-3 times a week
for routine tests.

Within 2 days before each cycle, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- You will complete the questionnaire about nervous system side effects.

- Your performance status will be recorded.

- Blood (about 2 tablespoons) will be drawn for routine tests.

After every 2 cycles, the following tests and procedures will be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- You will have a chest x-ray or CT scans to check the status of the disease. These
scans may be of your head, neck, chest, stomach, and/or pelvis. The CT scan at Cycle 4
will only occur if the doctor thinks it is needed.

- Blood (about 5 teaspoons) will be drawn for routine tests.

- If your doctor thinks it is needed, you will have a bone marrow biopsy/aspirate to
check the status of the disease.

- If your doctor thinks it is needed, you will have an ECHO or a MUGA scan and/or an ECG.

You will have an exam of the colon (colonoscopy) to check the status of the disease after
Cycle 2. Biopsy samples (about 3-6) of the colon will be taken during this exam to check
the status of the disease.

After Cycles 2, 6, and/or 8, if your doctor thinks it is needed, you will have a positron
emission tomography (PET) scan to check the status of the disease.

After Cycle 6, you will be taken off study if the disease is in "complete remission" (if the
disease has disappeared). Otherwise, you may receive 2 more cycles of study treatment.

If you are receiving 2 more cycles, if colonoscopy was done after Cycle 2 and it showed
lymphoma, you will have another colonoscopy after Cycle 6 and Cycle 8 to check the status
of the disease. Biopsy samples (about 3-6) of the colon will be taken during this exam to
check the status of the disease.

Length of Study:

You will receive the study drugs for up to 8 cycles (about 8 months). You will be taken off
study early if the disease gets worse or intolerable side effects occur before Cycle 8, or
if the disease is in complete remission after Cycle 6.

End-of-Treatment Visit:

After you have finished receiving the study drugs, the following tests and procedures will
be performed:

- You will have a physical exam, including measurement of your weight and vital signs.

- You will complete the questionnaire about nervous system side effects.

- Your performance status will be recorded.

- You will have a chest x-ray or CT scans to check the status of the disease.

- Blood (about 5 teaspoons) will be drawn for routine tests.

- If your doctor thinks it is needed, you will have a bone marrow biopsy/aspirate to
check the status of the disease.

- If your doctor thinks it is needed, you will have an ECHO or a MUGA scan and/or an ECG.

Follow-Up Visits:

After you have finished receiving the study drugs, you will have follow-up visits according
to the following schedule:

- Every 3 months during Year 1 after treatment.

- Every 4 months during Year 2 after treatment

- Every 6 months during Years 3-4 after treatment.

- Every 12 months after Year 4 after treatment.

At each of the follow-up visits, the following tests and procedures will be performed:

- You will have a complete physical exam, including measurement of your weight and vital
signs.

- You will complete the questionnaire about nervous system side effects.

- Your medical history will be recorded

- Your performance status will be recorded.

- Blood (around 1 tablespoon) will be drawn for routine tests.

- You will have a chest x-ray to check the status of the disease.

- You will have CT scans of the head, neck, chest, abdomen, and pelvis to check the
status of the disease.

- If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check
the status of the disease.

This is an investigational study. All of the drugs used in this study are FDA approved and
commercially available for the treatment of various types of lymphoma. The use of this drug
combination is investigational.

Up to 46 patients will take part in this multicenter study. All will be enrolled at M. D.
Anderson.


Inclusion Criteria:



1. Confirmed diagnosis mantle cell lymphoma and its variants, excluding marginal zone
and disease exclusively in the GI system. Patients should have measurable disease
based on Cheson Criteria or Bone Marrow/tissue sample positive for mantle cell
lymphoma. No prior therapy with a combination of bortezomib, cyclophosphamide and
rituximab.

2. Patients with performance status of 2 or less (Zubrod).

3. Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma;
ANC >1000/mm^3 and platelets >100,000/mm^3 unless due to lymphoma.

4. Cardiac ejection fraction 50% or greater.

5. Ages 18 to 85.

6. Patients must be willing to receive transfusions of blood products.

7. Signed consent form.

8. Voluntary written 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, is surgically sterilized or if they are of childbearing potential, agree to
practice 2 effective methods of contraception (i.e., a hormonal contraceptive,
intra-uterine device, diaphragm with spermicide, condom with spermicide, or
abstinence) from the time of signing the informed consent form through 30 days after
the last dose of VELCADE, or agree to completely abstain from heterosexual
intercourse.

10. Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to
1 of the following: practice effective barrier contraception during the entire study
treatment period and through a minimum of 30 days after the last dose of study drug,
or completely abstain from heterosexual intercourse.

Exclusion Criteria:

1. HIV infection.

2. CNS involvement.

3. Patient has a platelet count of < 100 K (eg <30 x 10^9/L for studies with bortezomib
alone) within 14 days before enrollment.

4. Patient has an absolute neutrophil count of ANC (eg <1.0 x 10^9/L for studies with
bortezomib alone)> within 14 days before enrollment.

5. Patient has > 1.5 X Total Bilirubin

6. Patient has a calculated or measured creatinine clearance of < 20 mL/minute
creatinine clearance (eg <20 mL/minute for studies with bortezomib alone) > within 14
days before enrollment.

7. Patient has >/= Grade 2 peripheral neuropathy within 14 days before enrollment.

8. 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.

9. Patient has hypersensitivity to bortezomib, boron or mannitol.

10. Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum Beta-human chorionic gonadotropin
(Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.

11. Participation in clinical trials with other investigational agents not included in
this trial, within 14 days the start of this trial and throughout the duration of
this trial.

12. Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

13. 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.

14. Concurrent or previous malignancy whose prognosis is poor (< 90% probability of
survival at 5 years).

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Response Rate

Outcome Time Frame:

Evaluation of disease after every 2 cycles.

Safety Issue:

No

Principal Investigator

Jorge Romaguera, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0057

NCT ID:

NCT00958256

Start Date:

August 2009

Completion Date:

Related Keywords:

  • Mantle Cell Lymphoma
  • Lymphoma
  • Mantle Cell Lymphoma
  • Lymphoma
  • Bortezomib
  • Velcade
  • Rituximab
  • Rituxan
  • Cyclophosphamide
  • Cytoxan
  • Neosar
  • Mesna
  • Mesnex
  • G-CSF
  • Filgrastim
  • Neupogen
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030