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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

Phase 3
18 Years
70 Years
Open (Enrolling)

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Trial Information

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

Central Venous Catheter Placement:

If you are found to be eligible to take part in this study, you will first have a central
venous catheter (CVC) placed. A CVC is a sterile flexible tube that will be placed into a
large vein while you are under local anesthesia. Your doctor will explain this procedure to
you in more detail, and you will be required to sign a separate consent form.

The chemotherapy, some of the other drugs in this study, and the stem cell transplant will
be given by vein through your CVC. Blood samples will also be drawn through your CVC. The
CVC will remain in your body during treatment.

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 be asked to
sign a separate consent form for the stem cell procedure.

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.


You will be asked to complete a quality-of-life questionnaire before starting the study
drugs and then once a week for 4 weeks 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

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

Up to 190 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

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

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.

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants with Complete Response (CR)

Outcome Description:

Complete response (CR), evaluated 90 days from transplant, defined as (i) negative immunofixation of the multiple myeloma (MM) protein in urine and serum, (ii) disappearance of any soft tissue plasmacytomas, and (iii) less than 5% plasma MM cells in the bone marrow. International Myeloma Working Group uniform response criteria.

Outcome Time Frame:

Evaluated 90 days from transplant.

Safety Issue:


Principal Investigator

Muzaffar H. Qazilbash, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

Related Keywords:

  • Myeloma
  • Myeloma
  • Multiple Myeloma
  • Light chain Multiple Myeloma
  • MM
  • Autologous Hematopoietic Stem Cell Transplantation
  • Busulfan
  • Busulfex
  • Myleran
  • Melphalan
  • Alkeran
  • G-CSF
  • Filgrastim
  • NeupogenTM
  • Questionnaire
  • Survey
  • Quality of Life
  • QOL
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



UT MD Anderson Cancer Center Houston, Texas  77030