Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide
Condition: Hematologic Diseases; Leukemia; Lymphoma; Myeloma
MeSH terms: Hematologic Diseases; Graft vs Host Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The goal of this clinical research study is to learn if cyclophosphamide given after busulfan
      and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which
      transplanted tissue attacks the body into which it is transplanted) in patients receiving a
      stem cell transplant. The safety of this drug combination will also be studied.
    

Detailed description: 
      The Study Drugs:

      Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer
      cells to die.

      Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may
      increase the likelihood of the cells dying.

      Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
      slow or stop their growth and spread throughout the body. This may cause the cancer cells to
      die. It is also designed to suppress the immune system and help prevent GVHD.

      Study Drug Administration and Transplant:

      If you are an inpatient, on Day -8 (8 days before the date of transplant), you will receive a
      low-level test dose of busulfan through a needle in your vein over 1 hour.

      If you are an outpatient, on Day -30 through Day -8, you will receive a low-level test dose
      of busulfan through a needle in your vein over 1 hour each day.

      You will be given an anti-seizure drug to help prevent seizures each time you receive
      busulfan. Your doctor will explain how the drug will be given and the drug's risks. Seizures
      are a rare but serious side effect of busulfan.

      On Days -8, -6, and -4, blood (about 1 teaspoon each time) will then be drawn a total of 11
      times for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the
      body at different time points. This PK testing will be done to find the dose of busulfan
      needed for your body size on the other days that you receive busulfan.

      On Day -6 through Day -3, you will receive your body-specific dose of busulfan by vein over 3
      hours each day. If you cannot have the blood level tests performed for any reason, you will
      receive the standard busulfan dose. You will receive fludarabine through a needle in your
      vein over 1 hour on each of these days before you receive busulfan.

      On Day 0, you will receive the donor bone marrow or blood stem cells by vein over about 1
      hour.

      On Day +3 and Day +4, you will receive cyclophosphamide by vein over 3 hours.

      On Days +3 thru +5 just before the first dose of cyclophosphamide and then every 4 hours, you
      will receive mesna by vein over 30 minutes for a total of 10 doses. Mesna is a drug that
      protects bladder cells from damage by chemotherapy drugs. It is used to decrease the risk of
      bleeding in the bladder.

      Once a day starting on Day +7, you will receive filgrastim (G-CSF -- a drug that helps with
      the growth of white blood cells) through a needle under your skin until your blood cell
      levels reach "recovered" levels for 3 days in a row.

      Study Visits:

      Every day you are in the hospital and at each outpatient visit, you will have a physical exam
      to check for symptoms of GVHD.

      Blood (about 3 teaspoons) will be drawn at least 2 times a week for the first 100 days after
      the transplant for routine tests.

      About 1 month after your transplant, then once every 3 months up to a year, the following
      tests and procedures will be performed:

        -  Blood (about 5 tablespoons) will be drawn for routine tests and to check for CMV. Blood
           draws may be repeated more often, if you doctor thinks it is needed.

        -  Urine will be collected for routine tests.

        -  You will have a bone marrow aspirate and biopsy to check the status of the disease.

      At Months 1, 2, 3, 6, and 12 after your transplant, blood (about 4 tablespoons) will be drawn
      to check the status of your immune system.

      Tests and procedures may be repeated more often during the study, if your doctor thinks it is
      needed.

      Length of Study:

      You will be on study in the hospital for about 4 weeks. You will be taken off study if the
      disease gets worse or if the study doctor thinks it is in your best interest.

      Long-Term Follow-Up:

      After the first 24 months, you will receive either a phone call or a letter from the study
      doctor or your regular doctor 1 time each year to check the status of the disease. If you are
      contacted by mail, you will be given a self-addressed stamped envelope with which you can
      return your responses to the doctor.

      This is an investigational study. Busulfan is FDA approved and commercially available for the
      treatment of chronic myelogenous leukemia (CML). Fludarabine is FDA approved and commercially
      available for the treatment of chronic lymphocytic leukemia (CLL). Cyclophosphamide is FDA
      approved and commercially available for the treatment of lymphoma. The use of these drugs
      together for the possible prevention of GVHD is investigational.

      Up to 40 participants will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Busulfan; Fludarabine; Cyclophosphamide
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.; Dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.; Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Other intervention name(s): Bulsulfex™; Myleran®; Fludarabine Phosphate; Fludara; Cytoxan®; Neosar®
Intervention MeSH terms: Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Post-allogeneic transplantation; Graft-versus-Host Disease Prophylaxis; Graft-versus-Host Disease; GVHD; Hematologic malignancies; Leukemia; Lymphoma; Myeloma; Human Leukocyte Antigen; HLA; Busulfan; Cyclophosphamide; Fludarabine; Mesna; Cytoxan®; Neosar®; Busulfex; Myleran®; Fludarabine Phosphate