Gemcitabine Plus Busulfan, Melphalan and Hematopoietic Cell Transplant for Advanced Lymphoid Malignancies
Condition: Leukemia; Lymphoma; Myeloma
MeSH terms: Lymphoma; Leukemia; Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to find the highest tolerated dose of gemcitabine
      that can be given with busulfan and melphalan. The safety of this drug combination will also
      be studied.
    

Detailed description: 
      Busulfan and melphalan are designed to kill cancer cells by binding to DNA (the genetic
      material of cells), which may cause cancer cells to die. They are commonly used in stem cell
      transplantation.

      Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells
      to die. It may help to increase the effect of busulfan and melphalan on the tumor cells, by
      not allowing these cells to repair the DNA damage caused by busulfan or melphalan.

      You will have apheresis done to collect some of your stem cells. Apheresis is the process of
      removing part of the blood (such as platelets or white blood cells) from the body in order to
      remove certain elements, such as stem cells. Then, the rest of the blood is returned back to
      your body. Your stem cells will be put back in your body after you finish receiving
      gemcitabine, busulfan, and melphalan. Apheresis will be done by a major vein through a
      central venous catheter (CVC), usually in the chest. 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 these procedures to you in more detail, and you will be required to sign a separate
      consent form for each procedure.

      If you are found to be eligible to take part in this study, you will be enrolled in a group
      of at least 2 participants to begin receiving the study drugs. The dose of the study drugs
      you receive will depend on when you enrolled in this study. If no intolerable side effects
      occur in your group, researchers will continue to enroll participants at the next highest
      dose level until the highest tolerable dose of the study drugs is found. The dose that you
      receive will remain the same throughout this study.

      Before you start to receive chemotherapy at treatment doses, you will be given a very small
      test dose of busulfan. Blood (1 teaspoon) will be drawn to check the levels of the drug in
      your blood at ten different timepoints (5-6 tablespoons total). This will help the study
      staff calculate your treatment doses of this drug. If there is a schedule conflict and the
      laboratory is not available for this testing, this procedure will not be performed. In that
      case, you would receive an unchanging dose of busulfan during the treatment.

      During Day 1 you will receive gemcitabine and busulfan by CVC.

      On Days 2-4, you will receive busulfan.

      On Day 5, you will not receive any study drugs.

      On Day 6, you will receive gemcitabine followed by melphalan.

      On Day 7, you will receive melphalan.

      On Day 8, you will not receive any study drugs.

      On Day 9, you will receive your autologous stem cells through a needle in your vein over
      about 30-60 minutes.

      If you have a B-cell cancer, you will receive rituximab (a treatment used for certain
      lymphomas or chronic lymphocytic leukemia) as part of standard of care, 1 day after and again
      8 days after the infusion of the autologous cells.

      As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your
      skin daily, starting 1 day after the transplant, until your blood cell levels return to
      normal.

      As part of standard care, you will receive a total of 6 doses of palifermin by vein. Three
      (3) of the doses will be given before starting chemotherapy (with a 24-hour break between the
      last dose of palifermin and the first dose of chemotherapy), and 3 doses will be given after
      the last chemotherapy dose, starting on Day 0.

      You will be taken off this study 100 days after the transplant. You may be taken off this
      study early if the disease gets worse or you experience any intolerable side effects.

      As part of standard care, you will remain in the hospital for about 3-4 weeks after
      transplantation. After you are released from the hospital, you will continue as an outpatient
      in the Houston area to be monitored for infections and transplant-related complications.

      This is an investigational study. Busulfan, gemcitabine, and melphalan are all FDA approved
      and commercially available. The use of these study drugs together and the use of gemcitabine
      at these dose levels is investigational. Up to 143 patients will take part in this study. All
      will be enrolled at M. D. Anderson.
    

Intervention name(s): Busulfan; Gemcitabine; Melphalan; Hematopoietic Cell Transplantation; Rituximab for Patients with B-Cell Malignancies; Palifermin
Intervention type(s): Drug; Drug; Drug; Other; Drug; Drug
Intervention description(s): Day -10 = 32 mg/m^2 Intravenous Test Dose; Days -8 thru -5 = 105 mg/m^2 Intravenous; Day -8 = 75 mg/m^2 Intravenous bolus; Day -3 = 75 mg/m^2 Intravenous bolus.; Day -3 and Day -2 = 60 mg/m^2 Intravenous.; Infusion of stem cells on Day 0.; 375 mg/m^2 Intravenous on Days 1 and 8.; 60 microgram/kg by vein on Days -13 to -11 and Days 0, +1, +2
Other intervention name(s): Busulfex; Myleran; Gemzar; Gemcitabine Hydrochloride; Alkeran; Stem Cell Infusion; HCT; Rituxan; Kepivance
Intervention MeSH terms: Rituximab; Gemcitabine; Melphalan; Busulfan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Lymphoid Malignancies; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Hematopoietic Cell Transplantation; Myeloma; Leukemia; Lymphoma; Busulfan; Busulfex; Myleran; Gemcitabine; Gemcitabine Hydrochloride; Gemzar; Melphalan; Alkeran