A Randomized Trial to Compare Busulfan + Melphalan 140 mg/m2 With Melphalan 200 mg/m2 as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the flip of a coin) to 1 of 2 study groups.

- Group 1 will receive melphalan and busulfan.

- Group 2 will receive melphalan.

Both groups will have a stem cell transplant.

Study Drug Administration:

If you are in Group 1, you will first receive an additional low-level "test" dose of busulfan
given by vein to check how your blood levels change over time. This information will be used
to decide the next dose that is needed to reach a target blood level of busulfan. Blood
(about 1 teaspoon each time) will be drawn up to 11 times during the next 11 hours after the
test dose and the first high-dose busulfan treatment.

A heparin lock line will be placed in a vein to lower the number of needle sticks needed for
these draws.

This test dose of busulfan can be given as an outpatient before you are admitted to the
hospital, or you will be admitted on Day -10 (10 days before your transplant) and will
receive the test dose on Day -9. If it is not possible for these blood level tests to be
performed for technical or scheduling reasons, you will receive the standard, fixed
(unchanging) dose of busulfan.

Eight (8) or 10 days before the transplant, you will be admitted to the hospital and given
hydration fluids by vein.

On Days -7, -6, -5, and -4, you will receive busulfan by vein over 3 hours. You will receive
melphalan on Days -2 and -1 by vein over 30 minutes. You will receive the stem cell
transplant through the CVC on Day 0.

If you are in Group 2, you may be admitted to the hospital 3 days before the transplant. You
will receive hydration fluids by vein. Two (2) days before the transplant, you will receive
melphalan by vein over 30 minutes. You will not receive melphalan the day before the
transplant.

Stem Cell Transplant:

The day that you receive the stem cell transplant is called Day 0. The stem cells will be
given by vein through the CVC. The cells will travel to your bone marrow where they are
designed to start making healthy, new blood cells after several weeks. You will sign a
separate consent for the collection of your stem cells.

Beginning 5 days after the transplant, you will receive filgrastim (G-CSF) through a needle
under your skin 1 time each day until your blood cell levels return to normal. Filgrastim is
designed to help with the growth of white blood cells.

You will be in the hospital after the transplant for about 2-4 weeks.

Questionnaire:

You will be asked to complete a quality-of-life questionnaire before starting the study drugs
and then once a week during Weeks 1, 2, and 4 after the stem cell transplant. The
questionnaire will take about 15 minutes to complete.

Follow-Up Visits:

About 3 months after the transplant, you will have a bone marrow aspiration and biopsy to
check the status of the disease. To collect a bone marrow aspiration and biopsy, an area of
the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn
through a large needle.

Every 3 months during the first year after the transplant, blood (about 1-2 tablespoons) will
be drawn to check your immune response and status of the disease.

About 1 year after the transplant, you will have a bone scan if the doctor thinks it is
needed.

Length of Study:

One (1) year after the transplant, your participation in this study will be over.

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 intolerable side effects after you
receive chemotherapy, then you will still have 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 doctor decides it is needed.

This is an investigational study. Busulfan and melphalan are commercially available and FDA
approved for the treatment of myeloma. The use of melphalan alone before an autologous stem
cell transplant is considered standard of care. Using busulfan with melphalan is
investigational.

Up to 205 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients with multiple myeloma in complete remission (CR), partial remission (PR), or
very good partial remission (VGPR), or symptomatic stable disease (no evidence of
progression) including patients with light chain MM detected in the serum by free
light chain assay.

2. Patients with non-secretory multiple myeloma [absence of a monoclonal protein (M
protein) in serum as measured by electrophoresis (SPEP) and immunofixation (SIFE) and
the absence of Bence Jones protein in the urine (UPEP) defined by use of conventional
electrophoresis and immunofixation (UIFE) techniques] but with measurable disease on
imaging studies like MRI, CT scan or PET scan.

3. Who have received at least two cycles of initial systemic therapy and are within 2 to
12 months of the first dose. Mobilization therapy is not considered initial therapy.

4. 70 years of age or younger.

5. Karnofsky performance score 70% or higher.

6. Cardiac function: left ventricular ejection fraction at rest > 40% within 3 months of
registration.

7. Hepatic function: bilirubin < 2x the upper limit of normal and ALT and AST < 2.5x the
upper limit of normal.

8. Renal function: creatinine clearance of >/= 40 mL/min, estimated or calculated.

9. Pulmonary function: DLCO, FEV1, FVC >/= 50% of predicted value (corrected for
hemoglobin) within 3 months of registration

10. Signed informed consent form.

Exclusion Criteria:

1. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
medication and progression of clinical symptoms).

2. Patients seropositive for the human immunodeficiency virus (HIV).

3. Patients with history of myocardial infarction within 6 months prior to enrollment or
has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities.

4. Patients participating in an investigational new drug protocol within 14 days before
enrollment.

5. Female patients who are pregnant (positive b-HCG) or breastfeeding.

6. Prior stem cell transplantation allogeneic or autologous.

7. Prior organ transplant requiring immunosuppressive therapy.