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
Condition: Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 3

Summary: 
      The goal of this clinical research study is to compare Busulfex (busulfan) with or without
      Alkeran (melphalan) to learn which study therapy may be better at helping to control MM in
      patients who will receive an autologous stem cell transplant. The safety of this combination
      therapy will also be studied.

      Melphalan and busulfan are designed to damage the DNA (genetic material) of cells, which may
      cause cancer cells to die.
    

Detailed description: 
      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.
    

Intervention name(s): Busulfan; Melphalan; Questionnaire; G-CSF; High Dose Melphalan; Stem cell transplant
Intervention type(s): Drug; Drug; Other; Drug; Drug; Procedure
Intervention description(s): Test dose (32 mg/m^2) on day -9 then 130 mg/m^2 by vein or adjusted dose on Days -7, -6, -5, and -4.; 70 mg/m2 by vein over 30 minutes minutes on Days -2 and -1.; Quality of Life (QOL) questionnaire before starting the study drugs and then once every 4 weeks after the stem cell transplant, taking about 15 minutes to complete.; Approximately 5 mcg/kg/day subcutaneously beginning on Day +5.; 200 mg/m2 by vein over 30 minutes on Day -2.; Stem cell infusion on Day 0.
Other intervention name(s): Busulfex; Myleran; Alkeran; Survey; Filgrastim; NeupogenTM; Alkeran; ABMT; autologous bone marrow transplantation; Peripheral Blood Progenitor Cells; PBPCs
Intervention MeSH terms: Melphalan; Busulfan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 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