Phase I/II Study of the Combination of Bortezomib With Arsenic Trioxide, Ascorbic Acid and High-Dose Melphalan for Patients With Multiple Myeloma
Melphalan is designed to damage the DNA of cells, which may cause cancer cells to die.
High-dose melphalan is considered the standard of care for multiple myeloma. Bortezomib is
designed to block a protein that plays a role in cell function and growth, which may cause
cancer cells to die. Arsenic trioxide may cause cancer cells to die, and researchers want
to find out if arsenic trioxide helps melphalan in killing cancer cells. Vitamin C makes
arsenic trioxide more available inside the cancer cells, and researchers want to learn if
Vitamin C makes arsenic trioxide more effective.
Before you can start treatment 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. You will have a
physical exam, including measurement of vital signs (blood pressure, heart rate,
temperature, and breathing rate). Your complete medical history will be recorded. You will
have a dental exam to check for any infected teeth or gums that may flare up after
You will have a bone marrow aspirate and biopsy. To collect a bone marrow aspirate/biopsy,
an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone
marrow is withdrawn through a large needle. Cytogenetic tests will be performed on the
aspirate sample to look for any genetic abnormalities in your DNA. You will have x-rays of
your bones taken. The study doctor will look at the x-rays to see if there are any
myeloma-related bone changes. You will also have a chest x-ray.
You will have blood (about 2 tablespoons) and urine collected for routine tests. You will
have a pulmonary function test, to check if your lungs are strong enough for high-dose
chemotherapy. You will have an electrocardiogram (ECG -- a test that measures the
electrical activity of the heart). You will also have a MUGA scan to evaluate the function
of your heart. Women who are able to have children must have a negative blood pregnancy
test. The blood will be drawn as part of the 2 tablespoons drawn at screening.
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of dice) to one of 3 treatment groups. There is an equal chance of being
assigned to any of the 3 groups. All 3 groups will receive melphalan, arsenic trioxide, and
Vitamin C. The second and third groups will also receive bortezomib, but at different dose
levels. The first 3 participants assigned to receive bortezomib on this study will receive
the lower of 2 bortezomib dose levels.
You will receive arsenic trioxide through a needle in a vein over 2 hours, once a day for 7
days (Days -9 to -3). At the same time, you will receive Vitamin C once a day through the
vein for 7 days. After you receive the arsenic trioxide on Days -4 and -3, you will receive
melphalan through the vein over 30 minutes.
If you are in Group 2 or 3, you will receive bortezomib by an intravenous (IV) push on Days
-9, -6, and -3. An IV push takes a short period of time (less than 1 minute).
You will receive standard inpatient and outpatient stem cell transplant care and testing.
You will have to sign a separate consent form that describes the transplant procedure and
its risks. Your stem cells will be reinfused 2 days after the last dose of melphalan. To
check for any side effects, you will have an ECG performed 14 days after the transplant.
If intolerable side effects from the chemotherapy occur or there is sign of disease after
the transplant, you will be taken off study. If you have already received melphalan and
side effects occur, then the transplant will happen. However, if intolerable side effects
develop before melphalan, then you may be taken off study without having the transplant. If
you are taken off study early, you still may need to return for routine post-transplant
follow-up visits, if your transplant physician decides it is necessary.
If there is no sign of disease after the transplant, you will have routine follow-up visits.
Blood (about 2 tablespoons) will be drawn for routine tests at least once a week during the
first month after the transplant, and then once every month for the next 3 months after
that. At about 3, 6, and 12 months after the transplant, you will have bone marrow biopsies
and aspirates performed to check the status of the disease. You will have blood (about 2
tablespoons) and urine collected for routine tests. At 12 months after the transplant, you
will have x-rays of your bones taken.
One (1) year after the transplant, your participation in this study will be over.
This is an investigational study. Bortezomib, arsenic trioxide, and melphalan are
commercially available and FDA-approved for use in patients with myeloma. However, their
use in combination with Vitamin C (also commercially available) is investigational. Up to 60
patients will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients Reaching Complete Response (CR)
Number of participants with CR at Day 180 who had maintained CR for at minimum of 4 weeks, and who had: No monoclonal protein in urine/serum when analyzed by immunofixation electrophoresis; bone marrow normal by morphological examination with <5% plasma cells, <1% aneuploid light chain restricted population by flow cytometry for DNA/cIg; and, while healing of bony lesion is not required, no new lytic lesion should appear. Further compression fracture of spine not considered progressive disease.
Baseline through Day 180, with assessments at Day 90 and Day 180
Muzaffar H. Qazilbash, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|