Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
Condition: Lymphoma
MeSH terms: Lymphoma; Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The goal of this clinical research study is to find the highest tolerable dose of vorinostat
      that can be given with gemcitabine, busulfan, and melphalan with a stem cell transplant.
      Researchers also want to learn about the safety and level of effectiveness of this
      combination.

      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.

      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 cancer cells by not
      allowing these cells to repair the DNA damage caused by busulfan or melphalan.

      Vorinostat is designed to open up the DNA and allow greater access to drugs that bind to DNA,
      such as gemcitabine, busulfan and melphalan.
    

Detailed description: 
      Study Groups:

      If you are found to be eligible to take part in this study, you will be enrolled in a group
      of at least 3 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 dose level until either the vorinostat reaches the dose level
      currently used alone without stem cell transplant, or the highest tolerable dose of this drug
      is found. The dose that you receive will remain the same throughout this study.

      Busulfan Test Dose:

      You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test
      dose of busulfan is to check how the level of busulfan in your blood levels changes over
      time. This information will be used to decide the next dose needed to reach the target blood
      level that matches your body size. You will most likely receive this as an outpatient during
      the week before you are admitted to the hospital. If it cannot be given as an outpatient, you
      will be admitted to the hospital on Day -11 (11 days before your stem cells are returned to
      your body) and the test dose will be given on Day -10.

      About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK)
      testing of busulfan. PK testing measures the amount of study drug in the body at different
      time points and will help the study doctor determine what your dose of busulfan should be on
      study. These blood samples will be drawn at various timepoints before you receive busulfan
      and over about the next 11 hours. The blood samples will be repeated again on the first day
      of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in
      your vein to lower the number of needle sticks needed for these draws. If it is not possible
      for the PK tests to be performed for technical or scheduling reasons, you will receive the
      standard fixed dose of busulfan.

      If you receive the busulfan test dose as an outpatient:

      On Days -12, -11, and -10, you will receive palifermin by vein over about 30 seconds each day
      to help decrease the risk of side effects in the mouth and throat.

      You will be admitted to the hospital on Day -9.

      If you receive the busulfan test dose as an inpatient:

      On Days -13, -12, and -11, you will receive palifermin by vein over about 30 seconds each day
      to help decrease the risk of side effects in the mouth and throat.

      You will be admitted to the hospital on Day -11.

      Study Drug Administration (for all patients):

      In stem cell transplant, the days before you receive your stem cells are called minus days.
      The day you receive the stem cells is called Day 0. The days after you receive your stem
      cells are called plus days.

      Beginning on Day -9, you will swish the liquids caphosol and glutamine in your mouth 4 times
      a day, for about 2 minutes each time. You will swish these liquids every day until you leave
      the hospital. These drugs are used to help decrease the risk of side effects in the mouth and
      throat.

      On Day -8 through Day -2, you will take vorinostat by mouth, with food.

      On Day -8, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and busulfan by vein
      over 3 hours.

      On Days -8, -7, -6, and -5, you will receive busulfan by vein over 3 hours.

      On Day -3, you will receive gemcitabine by vein over 3 1/2 - 4 1/2 hours and melphalan by
      vein over 30 minutes.

      On Day -2, you will receive melphalan by vein over 30 minutes.

      On Day -1, you will rest.

      On Day 0, you will receive your stem cells by vein over about 30-60 minutes.

      You will receive 3 more doses of palifermin by vein over 15-30 seconds on Days 0, +1 and +2.

      If you have a B-cell cancer, you will receive rituximab (a treatment used for certain
      lymphomas or chronic lymphocytic leukemia) by vein over 3-6 hours as part of standard of
      care, on Days +1 and +8.

      As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your
      skin 1 time a day starting on Day +5 until your blood cell levels return to normal.

      Study Tests:

      On Day -1, you will have an electrocardiogram (ECG) to check your heart function.

      About 30-100 days after the transplant, you will have lung function tests.

      About 100 days after the transplant:

        -  Blood (about 4 teaspoons) will be drawn for routine tests.

        -  If the doctor thinks it is needed, you may have a bone marrow aspiration and biopsy to
           check the status of the disease.

        -  You will have a CT scan of the neck, chest, abdomen, and pelvis to check the status of
           the disease.

        -  If the doctor thinks it is needed, you will have a PET scan to check the status of the
           disease.

      Length of Study:

      As part of standard care, you will remain in the hospital for about 3-4 weeks after the
      transplant. 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.

      You will be taken off study about 100 days after the transplant. You may be taken off study
      early if the disease gets worse, if intolerable side effects occur, or if you are unable to
      follow study directions.

      This is an investigational study. Vorinostat, gemcitabine, busulfan, melphalan, and rituximab
      are all FDA approved and commercially available. The use of these study drugs in combination
      is investigational.

      Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
    

Intervention name(s): Vorinostat; Gemcitabine; Busulfan; Melphalan; Stem Cell Infusion; Rituximab; G-CSF; Palifermin; Dexamethasone acetate
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Drug; Drug; Drug; Drug
Intervention description(s): Starting dose: 200 mg by mouth on Days -8 to -2.; Starting dose: 2175 mg/m2 by vein on Days -8 and -3. This includes the gemcitabine 75 mg/m2 loading dose.; AUC: 4,000 micrometer (microM).min/day, or 105 mg/m2/day) on Days -8 to -5.
Pharmacokinetics will be performed with the first dose of 32 mg/m2 by vein on Day -8. The doses on Days -6 and -5 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5.; 60 mg/m2 by vein on Days -3 and -2.; Infusion of stem cells by vein on Day 0.; 375 mg/m2 on days +1 and +8 for patients with CD20+ tumors.; 5 mcg/kg/day (rounded up the nearest vial) subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.; 60 mcg/kg by vein daily for 6 doses. Three doses administrated prior to start chemo (24 hours must elapse between the last dose and first therapeutic dose of chemo) and three doses after the last chemo starting on day 0.; 8 mg by vein twice a day from day -8 AM to day -2 PM.
Other intervention name(s): SAHA; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza; Gemcitabine Hydrochloride; Gemzar; Busulfex; Myleran; Alkeran; Rituxan; Filgrastim; NeupogenTM; Kepivance; Decadron
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Rituximab; Gemcitabine; Melphalan; Busulfan; Vorinostat; BB 1101
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Lymphoma; Lymphoid malignancies; Relapsed; Refractory; Autologous hematopoietic cell support; Stem cell infusion; Hodgkin's lymphoma; non-Hodgkin's lymphoma; Vorinostat; SAHA; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza; Busulfan; Busulfex; Myleran; Gemcitabine; Gemcitabine Hydrochloride; Gemzar; Melphalan; Alkeran; Rituximab; Rituxan; Dexamethasone; Decadron; G-CSF; Filgrastim; NeupogenTM; Palifermin; Kepivance