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

Phase 1/Phase 2
75 Years
Not Enrolling

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Trial Information

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marrow is withdrawn through a large needle.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.

Inclusion Criteria:

1. a) Primary Refractory Disease (defined as failure to achieve even a partial response
to induction therapy) b) Consolidation of a partial remission (defined as a decrease
but continued presence of monoclonal protein on serum and urine immunofixation
electrophoresis, and/or the presence of plasmacytosis on bone marrow aspirate and
biopsy) c) Relapsing after prior therapy (disease relapsing after achieving a partial
or complete response to prior conventional or high-dose therapy).

2. Age up to 75 years.

3. Zubrod performance status of <2.

4. Left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic
cardiac disease.

5. Forced expiratory volume (FEV1), forced volume vital capacity (FVC) and Diffusing
Capacity of the Lung for Carbon Monoxide (DLCO) >40%. No symptomatic pulmonary

6. Serum bilirubin <2 times upper limit of normal, alanine aminotransferase/SGPT <4
times upper limit of normal. No evidence of chronic active hepatitis or cirrhosis. No
effusion or ascites >1L prior to drainage.

7. HIV-negative.

8. Negative Beta human chorionic gonadotrophin (hCG) test in a woman with child bearing
potential, defined as not post-menopausal for 12 months or no previous surgical

9. Patient or guardian able to sign informed consent

10. Corrected QT interval less than 470 msec.

Exclusion Criteria:

1. Corrected QT interval greater than 470 msec.

2. Patients in complete remission (defined as the absence of monoclonal protein on serum
and urine immunofixation electrophoresis, and the absence of plasmacytosis in bone
marrow aspirate and biopsy).

3. Patients with non-secretory myeloma.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients Reaching Complete Response (CR)

Outcome Description:

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.

Outcome Time Frame:

Baseline through Day 180, with assessments at Day 90 and Day 180

Safety Issue:


Principal Investigator

Muzaffar H. Qazilbash, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2006

Completion Date:

December 2008

Related Keywords:

  • Myeloma
  • Multiple Myeloma
  • Melphalan
  • Trisenox
  • Arsenic Trioxide
  • Ascorbic Acid
  • Vitamin C
  • Velcade
  • Bortezomib
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



UT MD Anderson Cancer Center Houston, Texas  77030