Busulfan Plus Melphalan Conditioning Regimen for Lymphoid Malignancies or Multiple Myeloma
Condition: Multiple Myeloma; Lymphoma
MeSH terms: Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Primary Objectives:

        1. To determine the efficacy of administering multiple doses of intravenous (i.v.) busulfan
           at a dose of 130 mg/m2, to yield a systemic plasma drug exposure represented by a daily
           area under the plasma concentration versus time curve (AUC) of approximately 5,000
           mMol-min for 4 days, followed by i.v. melphalan at a dose of 70 mg/m2 for 2 days in
           adult patients receiving autologous or allogeneic transplantation for lymphoid
           malignancies or myeloma.

        2. To describe the plasma pharmacokinetic (PK) profiles of busulfan and melphalan in this
           regimen.

        3. To determine the disease-free and overall survival of patients receiving this
           preparative regimen.

        4. To determine the treatment-related morbidity and mortality of this combination of drugs.
    

Detailed description: 
      Busulfan and melphalan are both traditional alkylating agents that are designed to interfere
      with the production of cancer cells at the DNA (deoxyribonucleic acid) and RNA (ribonucleic
      acid) level.

      Before you can start treatment on this study, you will have what are called "screening
      tests". These tests will help the doctor decide if you are eligible to take part in the
      study. You will have a complete physical exam, including routine blood (2-3 teaspoons) and
      urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone
      marrow biopsy. Women who are able to have children must have a negative blood pregnancy test.

      If you are found to be eligible to take part in this study, you will be able to start
      receiving chemotherapy treatment with busulfan and melphalan. Participants who agree to the
      optional blood draws described above will at first receive a therapeutic "trial dose" of
      busulfan by vein to test the blood levels over time. This therapeutic trial dose of busulfan
      is about 25% (1 fourth) of the full therapeutic dose of the drug. This information will be
      used to decide what the future high-dose busulfan treatments you receive will be. If you do
      not agree to the optional blood draw, you will receive a fixed amount of high-dose busulfan
      from the start.

      On the 1st day of hospitalization, you will receive fluids by vein through a central venous
      catheter. If you choose the optional busulfan dose for pharmacokinetic-based busulfan dosing,
      you will receive the optional busulfan dose 9 days before stem cell infusion (Day 1),
      followed by a rest day on Day 2. If you choose to receive a fixed dose of busulfan, busulfan
      will be injected through a central venous catheter over 3 hours, once a day, for the next 4
      days (Days 3-6, ending 3 days before the stem cell infusion day).

      Patients receiving pharmacokinetic-based dosing of busulfan will also continue to receive
      busulfan on Days 3-6. This will be followed by melphalan for all patients, given through your
      central venous catheter over 30 minutes, once a day, for 2 days, on days 8 and 9. Your stem
      cell infusion day will be on Day 10 of treatment.

      Patients receiving 5 out of 6 antigen matched-related allogeneic stem cell transplants or
      unrelated allogeneic stem cell transplants will also receive antithymocyte globulin (ATG), by
      vein, on Days 7-9, up to one day before the stem cell infusion. This is given to decrease the
      risk of GVHD and graft rejection in mismatched transplants.

      On Day 10, healthy blood stem cells or bone marrow from the donor will be given through the
      central catheter. This is your transplant date. You will also receive several other
      medications to help the treatment work and to help prevent infections while your immune
      system is weak. Tacrolimus and methotrexate will be given to decrease the risk of
      graft-versus-host-disease (GVHD). GVHD occurs when the donor's immune cells fight the
      patient's body. The tacrolimus will be started on the day before the transplant and will
      continue for up to six months. Tacrolimus is given by vein at first and then by mouth when
      you are able to eat. Methotrexate is given by vein on Days 11, 13, 16, and possibly on Day
      21, up to 11 days after the transplant.

      Please note that the treatment dates listed above were used to help explain your general
      treatment plan. By standard medical convention, the day of stem cell infusion is always
      listed as day zero. Therefore, the days listed above are different from the treatment plan
      described in the protocol and abstract.

      Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given
      by mouth when the counts are good. Pentamidine is given by vein when the counts are low.
      Acyclovir will be given at first by vein and then Valtrex (valacyclovir) will be given by
      pill to decrease the risk of viral infections. Granulocyte colony-stimulating factor (G-CSF)
      will be given to help the new bone marrow grow. It is given as an injection under the skin
      after the transplant. It will continue until the white blood cells reach an acceptable level.
      Overall, some of these drugs will be given for as long as 6 months or possibly longer. Other
      medications may be necessary. If you are allergic to some of these drugs, changes will be
      made.

      You will be in the hospital for about 3-4 weeks. You will have checkups every day until
      discharged from the hospital. You will then be seen in the outpatient clinic at least 3 times
      a week until your blood counts improve. You will be seen by your doctor at least every week
      until 100 days after the bone marrow transplant. You must stay in Houston during this time.
      After 100 days, you will return to the clinic according to your individual physician's
      recommendations.

      Some patients may need to receive spinal taps with instillation of chemotherapy several times
      over the year after transplantation. This is only for patients with a previous clinical
      history of leukemic involvement of the brain or high risk of developing leukemia relapse in
      the brain. The spinal tap is performed in the clinic. You are given local anesthetic at the
      lower back site, a small needle is inserted in the space between 2 spinal bones, a small
      amount of fluid that bathes the brain (cerebrospinal fluid) is removed for testing, and a
      small amount of chemotherapy is given.

      Bone marrow samples will be taken at about 1 month and 3 months after the transplant. You
      will also have a lung function test at 3 months after the transplant.

      This is an investigational study. The FDA has approved all of the drugs used in this study
      for use in stem cell transplantation. Up to 168 patients will take part in this study. All
      will be enrolled at M. D. Anderson.
    

Intervention name(s): Busulfan; Melphalan
Intervention type(s): Drug; Drug
Intervention description(s): Test Dose = 32 mg/m^2 IV for 1 Day; 130 mg/m^2 IV for 4 Days; 70 mg/m^2 IV for 2 Days
Other intervention name(s): Busulfex
Intervention MeSH terms: Melphalan; Busulfan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Myeloma; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Leukemia; Lymphoma; Busulfan; Melphalan; Autologous bone marrow; BMT; Peripheral blood stem cell transplant; PBSCT