Phase-I Study of Bortezomib (VELCADE) Plus ICE (Ifosfamide, Carboplatin, Etoposide) for Patients With Relapsed Classical Hodgkin Lymphoma
Bortezomib is designed to block a protein that plays a role in cell function and growth,
which may cause cancer cells to die.
ICE is a combination of chemotherapy drugs that, together, may work more effectively at
causing cancer cells to die by stopping cells from dividing.
Mesna is a drug that protects bladder cells from damage by the chemotherapy drug ifosfamide.
It is used to decrease the risk of bleeding in the bladder.
Before you can start taking the drugs on this study, you will have "screening tests." These
tests will help the doctor decide if you are eligible to take part in this study. These
tests may be performed within 28 days of starting the study drugs. If you have had some of
these exams, tests, or procedures performed recently, they may not need to be repeated.
This will be for your study doctor to decide. You will have a physical exam, including
measurement of your vital signs (blood pressure, heart rate, temperature, and breathing
rate), height, and weight. You will have x-rays and a bone marrow biopsy to check the
status of the disease. To collect a bone marrow biopsy, an area of the hip or chest bone is
numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a
large needle. You will have a computed tomography (CT) scan of your abdomen, chest, and
pelvis and a positron emission tomography (PET) scan. Blood (about 2-3 tablespoons) will be
drawn for routine tests. Women who are able to have children must have a negative blood
(about 1 teaspoon) pregnancy test within 1 month before starting therapy on this study.
Because taking part in this study requires that participants' ability to fight off
infections be normal, you will have blood drawn (about 1-2 tablespoons) to be tested for HIV
within 6 months before starting therapy on this study. If your HIV test results are found
to be positive, you will not be able to take part in this study.
All participants will receive bortezomib as a fixed dose, which will not change unless any
intolerable side effects occur. At the start of this study, 3 participants will be given a
dose of bortezomib. If this dose does not cause intolerable side effects, the dose will be
increased as new participants take part in this study. There will be a total of 3 groups
(with 3-6 participants per group) entered at increasing dose levels. The dose of bortezomib
you receive will depend on when you join this study.
If you are found to be eligible to take part in this study, you will receive bortezomib plus
ICE by vein. You will receive bortezomib, on Days 1 and 4, over 5 seconds. The ICE regimen
will be given as a continuous infusion over different times as follows. On Day 1, you will
receive ifosfamide and mesna over 24 hours. On Day 2, you will receive mesna over 12 hours
and carboplatin over 1 hour. On Days 1-3, you will receive etoposide over 2 hours. This
schedule for bortezomib plus ICE is considered 1 cycle (2 weeks) and will be repeated every
You may have 3-6 cycles of the study drugs, depending on your tolerance of the drugs and the
status of the disease. If the disease gets worse or you experience any intolerable side
effects, you will be taken off this study.
Blood (about 2-3 tablespoons) will be drawn once a week for routine tests. You will have a
study visit before the start of each 2-week cycle. During these visits, you will have a
brief questionnaire that will ask about specific side effects you might be experiencing. It
should take about 5 minutes to complete this questionnaire.
After completing 3 cycles, you will return for CT scans, bone marrow biopsies (if they were
positive for disease before you began on this study), and a PET scan to check the status of
After completing 3 cycles (if the disease did not worsen and intolerable side effects did
not occur), you may continue on this study for 3 more cycles. During Cycles 4-6, you will
have the same scans and blood tests as mentioned above.
After completing this study, for every 3-4 months on an indefinite basis, you will have
follow-up visits. During these visits, you will have blood drawn (about 2-3 tablespoons)
for routine tests. You will also have the same scans that were performed during the
This is an investigational study. Bortezomib and ICE are FDA approved and commercially
available. The combination of bortezomib plus ICE is considered investigational and
authorized for use in research only.
Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerable Dose (MTD) of Bortezomib when given in combination with ICE chemotherapy in participants with relapsed and refractory classical Hodgkin lymphoma (HL)
MTD dose escalation stops either at the highest indicated dose of bortezomib (1.5 mg/m2), or when a Dose limiting toxicity (DLT) has been observed in at least one third of the patients at any dose level.
Michelle A. Fanale, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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