Trial Information

Phase I/II Study of the Combination of Arsenic Trioxide With Ascorbic Acid and High-Dose Melphalan for Patients With Multiple Myeloma

Treatment:

High-dose melphalan followed by a transplant of autologous stem cells is thought to be one
of the most effective ways to treat multiple myeloma. However, the number one cause of
treatment failure in these patients is the disease coming back.

High-dose melphalan has been used in multiple myeloma for more than two decades and is
considered the standard of care for this disease. Recent research in the laboratory and
clinical trials has shown that Arsenic trioxide is an effective treatment against multiple
myeloma. It leads to tumor cell death in myeloma cell lines and in myeloma patients. Arsenic
trioxide can also make melphalan a more effective antimyeloma agent. This research has also
shown that vitamin C enhances the anti-myeloma activity of arsenic trioxide by making it
more toxic to myeloma cells. The purpose of this study is to learn if a combination of
arsenic trioxide, vitamin C, and melphalan will be safe, well-tolerated and effective in
myeloma patients.

Before treatment begins, you will have several tests performed to study the status of the
disease before you begin taking the study medication. You will have a bone marrow aspirate
and biopsies. An aspirate is the drawing of liquid marrow with a syringe, while a biopsy is
the removal of a small core of bone with a hollow needle. Aspirate can be done from the hip
bone or chest, while biopsy is always from the hip bone. You will have cytogenic tests, to
see if there are any genetic abnormalities in your DNA. You will have a bone survey done,
where the doctor will look at X-rays of your bones for any myeloma-related bone changes.

You will have routine and specialized blood tests done (about 2 tablespoons), to measure
blood counts, platelets, blood clotting, kidney function, electrolyte counts, and levels of
disease in your blood. You will also have a urine test to measure level of myeloma in your
urine. You will have a pulmonary function test, to check if your lungs is strong enough to
withstand high-dose chemotherapy. You will have an initial electrocardiogram (EKG) and also
a MUGA scan that will measure how strong your heart functions are.

Women who are able to have children must have a negative blood pregnancy test before
participating in this study.

If you agree and are eligible, you will be assigned to receive one of 3 arms. In the first
arm only melphalan and vitamin C, but no Arsenic trioxide will be given. In the second and
third arms, doses of arsenic trioxide together with Vitamin C and melphalan will be given.
Not all patients in this study will get the same dose of arsenic. Your dose assignment will
depend on the experience of other patients with this combination. The first 3 patients on
this study will get the lowest dose of arsenic trioxide.

Arsenic trioxide will be given through a needle in the vein over a period of 2 hours, once a
day for 7 days. At the same time, vitamin C will be given once a day through the vein for 7
days. On the last 2 days of arsenic trioxide treatment, melphalan will be given through the
vein over one hour after the arsenic. You will have your stem cells reinfused 2 days after
the last dose of melphalan.

Some patients agreeing to the optional procedure will receive one of the doses of melphalan
before starting the arsenic.

You will receive standard inpatient and outpatient transplant care and testing. This
involves blood and bone marrow tests, heart tests, lung tests and x-rays before the study
drug treatment and the transplant. To collect a bone marrow sample, 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. Blood tests (about two tablespoons) will be drawn at least once a week for
the first month after the transplant, and then once every month for the next 3 months.

Bone marrow biopsies and tests to check the level of myeloma protein in the urine and the
blood are also performed at 3, 6 and 12 months after the transplant.

You will be taken off study one year after transplant, if your disease does not come back.
Patients off study will still return for their routine post-transplant follow up visits as
decided by their transplant physician. If your disease comes back or intolerable side
effects occur, you will be taken off study.

This is an investigational study. Both arsenic trioxide and melphalan are commercially
available and have been approved for use in patients with myeloma, though their use together
with vitamin C is investigational. About 32 patients are expected to participate in this
study. All will be enrolled at UTMDACC.