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Bortezomib (Velcade) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies

Phase 2
70 Years
Open (Enrolling)

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Trial Information

Bortezomib (Velcade) and Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoid Malignancies

Carmustine, etoposide, cytarabine, and melphalan are designed to kill lymphoma cells by
inserting into the cell DNA. Rituximab is a monoclonal antibody that targets a specific
marker on the surface of lymphoma cells and causes it to die. Bortezomib works by blocking
proteasomes, which are clusters of proteins necessary for cancer cell growth. Cancer cells
may be sensitive to drugs like bortezomib because tumor cells have more proteins than normal
cells. Bortezomib enters the tumor cells and affects the way they divide. When cancer
cells cannot divide, they die.

If you are found to be eligible to take part in this study, you will receive carmustine
through a needle in your vein over 1 hour on Day 1. On Days 2-5 you will be given
cytarabine by vein over 1 hour and etoposide by vein over 3 hours. This will be repeated
every 12 hours on Days 2-5. On Day 6 you will be given melphalan by vein over 30 minutes.
On Day 7 the stem cells that were collected earlier from a donor will be given back to you
("transplanted") through your catheter over 30-45 minutes. You will also receive rituximab
by vein, over 5 to 7 hours before the transplant and then weekly, for a total of 4 doses.
In addition, if you are receiving a matched unrelated or mismatched donor transplant, on
days 5-6 you will also be given thymoglobulin by vein over 4-6 hours. Patients with T-cell
lymphoma will not receive Rituxan.

Bortezomib will be given by vein over 1 minute 13 days, 6 days, and 1 day before the
transplant, and again 2 days after the transplant.

G-CSF will be injected under the skin once a day until the your blood counts return to a
normal level, starting 7 days after the transplant.

Sometimes the infused donor cells cause inflammation of the skin, liver, and gut, and a
reaction called graft-versus-host disease (GVHD) occurs. To prevent GVHD, tacrolimus will be
given by vein non-stop starting 2 days before the transplant. It will be changed to oral
tablets before you leave the hospital. You will take tacrolimus for about 6-8 months after
the transplant. Methotrexate will be given for the same purpose on Days 1, 3, and 6 after
the transplant by vein over a few minutes. Patients receiving a matched unrelated or
mismatched donor will also be given methotrexate on day 11 after the transplant.

You will be required to stay in the hospital from about 2 weeks before the transplant until
about 2-3 weeks after the transplant. You must stay in the Houston area for about 100 days
after the transplant.

During the first 100 days after transplantation, blood (about 6 teaspoons) will be drawn for
routine tests. Blood (about 20-30 teaspoons) will also be drawn daily while you are in the
hospital to check the effect of the transplant. You will receive transfusions of blood and
platelets as needed. You will have a bone marrow biopsy/aspirate and/or chest x-ray if your
doctor thinks it is necessary.

Beginning 1 month after transplantation, then every 3 months for 1 year, and then every 6
months for 5 years, you will have CT scans, positron emission tomography (PET) or Gallium
scans (a nuclear medicine test that uses a special camera to take pictures of special
tissues), and a bone marrow biopsy/aspirate. These tests will be done to check the status of
the disease.

You will be on active study for 5 years after the transplant. You will be taken off study if
the disease gets worse or intolerable side effects occur.

You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine post-transplant follow-up visits,
if your transplant doctor decides it is needed.

It may be life-threatening to leave the study early during the conditioning regimen without
following up with the stem cell transplant, because your blood cell counts may be
dangerously low.

This is an investigational study. Bortezomib and rituximab are FDA approved and
commercially available. Their use in this study, however, is investigational since it is
used with transplantation. All other chemotherapy drugs are FDA approved and commercially
available. Up to 52 patients will take part in this study. All will be enrolled at MD

Inclusion Criteria:

1. Up to 70 years of age.

2. Any histological subtype of CD20+ lymphoid malignancies or T-cell lymphoid

3. Patients with CD20+ lymphoid malignancies in relapse after failing >/= 1 prior
regimen of conventional treatment and not eligible for non-myeloablative transplant.
Patients with T-Cell lymphoid malignancies can either be in relapse or newly
diagnosed with high risk features (such as high IPI of >/= 2).

4. Patients with prior non-myeloablative transplant are eligible if not from the same

5. A fully-matched or one-antigen mismatched sibling or unrelated donor.

6. Left ventricular EF >/= 40% with no uncontrolled arrythmias or symptomatic heart

7. FEV1, FVC and DLCO >/= 40%.

8. Serum creatinine < 1.8 mg/dL. Serum bilirubin < 3X upper limit of normal,

9. SGPT < 3X upper limit of normal.

10. Voluntary signed, 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.

11. Men and women of reproductive potential must agree to follow accepted birth control
methods for the duration of the study. 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. Male subject agrees to
use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

1. Past history of anaphylaxis following exposure to rituximab or VELCADE®, boron or

2. History of grade 3 or 4 NCI toxicity with prior VELCADE® therapy

3. Patient with active CNS disease.

4. Pregnant (Positive Beta HCG test in a woman with child bearing potential defined as
not post-menopausal for 12 months or no previous surgical sterilization) or currently
breast feeding. Pregnancy testing is not required for post-menopausal or surgically
sterilized women.

5. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.

6. Patients with other malignancies diagnosed within 2 years prior to Study Day -13
(except skin squamous or basal cell carcinoma).

7. Active uncontrolled bacterial, viral or fungal infections.

8. Major surgical procedure or significant traumatic injury within 4 weeks prior to Day

9. Serious, non-healing wound, ulcer, or bone fracture.

10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 3 months prior to Day -13.

11. History of Stroke within 6 months.

12. Myocardial infarction within the past 6 months prior to Study Day 1, or has New York
Heart Association (NYHA) Class III or IV heart failure or arrythmia, unstable angina,
uncontrolled congestive heart failure or arrythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities.Prior to study entry, any
ECG abnormality at screening must be documented by investigator as not medically

13. Uncontrolled hypertension(>/=140/90) .

14. Uncontrolled chronic diarrhea.

15. A prior allogeneic transplant from the same donor.

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

17. Patient has received other investigational drugs within 3 weeks before enrollment.

18. Active peripheral neuropathy greater or equal to grade 2.

Type of Study:


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:

90 days after the start of treatment

Safety Issue:


Principal Investigator

Issa F. Khouri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

February 2007

Completion Date:

Related Keywords:

  • Lymphoma
  • Lymphoma
  • Bortezomib
  • Velcade
  • LDP-341
  • MLN341
  • PS-341
  • Carmustine
  • Cytarabine
  • Etoposide
  • Melphalan
  • Rituximab
  • BEAM
  • BCNU
  • BiCNU®
  • ARA-C
  • Cytosar
  • DepoCyt®
  • Cytosine arabinosine hydrochloride
  • VePesid®
  • Rituxan
  • Lymphoma



UT MD Anderson Cancer Center Houston, Texas  77030