Allo Transplantation With Mylotarg, Fludarabine and Melphalan for AML, CML and MDS
Condition: Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Preleukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The goal of this clinical research study is to find the highest safe dose of Mylotarg that
      can be combined with chemotherapy in patients receiving allogeneic bone marrow
      transplantation. Researchers will study the effects of this treatment combination on patients
      with high-risk acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome.

      Primary Objective:

      1. To determine the safety and maximum tolerated dose of Mylotarg as part of a
      reduced-intensity preparative regimen patients undergoing related, mismatched-related or
      matched unrelated donor transplantation.

      Secondary Objectives:

        1. To evaluate response rates, engraftment kinetics and degree of chimerism achievable with
           this strategy.

        2. To evaluate the incidence and severity of GVHD in this population

        3. To evaluate disease-free and overall survival and relapse rates.
    

Detailed description: 
      Before treatment starts, patients will have a complete physical exam, including blood 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 will have a pregnancy test.

      In this study, patients will receive Mylotarg twelve days before the transplant. The first
      patients will receive Mylotarg at the lowest dose level. As the study continues, the dose
      levels will be increased as long as no severe side effects occur. Mylotarg may be given in
      the outpatient Ambulatory Treatment Center (ATC). Patients will be monitored in the ATC for
      eight hours on the day of infusion. For the next 5 days, patients will be evaluated in the
      Clinic on a daily basis or as per physician orders. One week before the transplant, all
      patients will be admitted to the hospital and will continue their treatment as inpatients.
      Patients experiencing side effects from their leukemia or leukemia treatment may need to be
      hospitalized earlier.

      On the 1st day of hospitalization, patients will receive fluids by vein. On the 5th, 4th, 3rd
      and 2nd day before the transplant, patients will receive Fludarabine, by vein. Melphalan will
      be given by vein on the 2nd day before transplant. Patients receiving five out of six antigen
      matched or unrelated bone marrow will also receive antithymocyte globulin, by vein, on the
      3rd, 2nd and 1st day before transplant.

      On the 7th day, healthy blood stem cells or bone marrow from the donor will be given through
      the central catheter. Some donor bone marrow or stem cells may be saved for future therapies.

      Patients will also receive several other medications to help the treatment work and to help
      prevent infections while their immune system is weak. Tacrolimus and methotrexate will be
      given to prevent 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 patients are able to eat. Methotrexate is given by vein on days 1, 3, 6 and possibly on
      day 11 after the transplant.

      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 will be given by pill to prevent
      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 beginning on the 7th day after
      the transplant. It will continue until the patient's 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.

      Patients will be in the hospital for about 3-4 weeks. Patients will have checkups every day
      until discharged from the hospital then 3 times a week until their blood counts improve.
      Patients will then be seen by their doctor at least every week until 100 days after the bone
      marrow transplant. Patients must stay in Houston during this time. After 100 days, patients
      will return at least every 3 months for the first year, then every 6 months for an additional
      two years.

      Bone marrow samples will be taken at about 1 month, 3 months, 6 and 12 months after the
      transplant.

      This is an investigational study. All of the drugs in this study are approved by the FDA.
      About 47 patients will take part in this study. All will be enrolled at M. D. Anderson.
    

Intervention name(s): Mylotarg; Fludarabine; Melphalan; Anti-thymocyte globulin; Stem cell transplant
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Starting dose 2 mg/m^2 over 2-hour intravenous infusion on day -12.; 30 mg/m^2 will be given intravenously daily at the same time over 30 minutes on days -5, -4, -3, -2.; 140 mg/m^2 will be given intravenously over 20 minutes starting 2 hours after the beginning of the fludarabine infusion on day -2.; Patients with an unrelated or mismatched related donor will receive 0.5 mg/kg on day -3 and 1.25 mg/Kg on days -2 and -1, following the chemotherapy.; Allogeneic Bone Marrow and Peripheral Blood Stem Cell Transplantation: Infusion of blood stem cells or bone marrow cells on day 0.
Other intervention name(s): Gemtuzumab; Gemtuzumab ozogamicin; Fludara; Fludarabine Phosphate; Alkeran; Rabbit anti-thymocyte globulin; Anti-thymocyte globulin (ATG); alloBMT; Allo PBSCT
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Gemtuzumab; Antilymphocyte Serum; Thymoglobulin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Myelogenous leukemia; AML; Myelodysplastic Syndrome; MDS; Chronic Lymphocytic Leukemia; CML; Mylotarg; Gemtuzumab; Gemtuzumab ozogamicin; Melphalan; Alkeran; Fludarabine Phosphate; Fludarabine; Fludara; Anti-thymocyte globulin; ATG; Allogeneic Bone Marrow; Peripheral Blood Stem Cell Transplantation; Allo PBSCT; Allogeneic transplantation