A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will evaluate the safety and effectiveness of a genetically engineered antibody,
      alemtuzumab (Campath[R]) on patients with myelodysplastic syndrome. MDS is made up of
      malignant stem cell disorders that can mean low levels of red blood cells-that is, anemia-and
      low counts of white blood cells and platelets. Patients with MDS are at risk for infection,
      spontaneous bleeding, and possible progression to leukemia, a cancer of bone marrow. Although
      bone marrow can produce some blood cells, patients with MDS experience a decrease in
      production of blood cells. Alemtuzumab recognizes specific types of white cells called
      lymphocytes and destroys them. This study will examine not only the usefulness of the
      medication but also the side effects in patients with MDS.

      Patients ages 18 to 72 who have MDS that requires transfusions and who do not have HIV or a
      life expectancy of less than 6 months may be eligible for this study. Screening tests include
      a complete physical examination and medical history. There will be a collection of about 8
      tablespoons of blood for analysis of blood counts as well as liver, kidney, and thyroid
      function; a pregnancy test; an electrocardiogram (EKG) to measure electrical activity of the
      heartbeat; an echocardiogram (ECHO), which uses sound waves to evaluate heart function;
      wearing of a Holter monitor for 24 hours while the electrical activity of the heart is
      recorded; and a bone marrow biopsy. Patients should not receive any vaccines when taking
      alemtuzumab or for at least 12 months after the last dose. In addition, patients should not
      take the herbal supplements Echinacea purpurea or Usnea 2 weeks before beginning the study
      and during it.

      For the study, all patients will receive a test dose of 1 mg of alemtuzumab infused into a
      vein during the course of 1 hour. If the dose is tolerated, the medication will be given at
      10 mg doses into the vein for 10 days, as an infusion of 2 hours. Blood samples of 2
      tablespoons will be taken daily, and vital signs will be measured daily. The ECHO and 24-hour
      Holter monitoring will be repeated after patients receive the last dose of the medication.
      Because suppression of the immune system results from a decrease in white cells that fight
      infections, patients will take medications to protect them against infections and to treat
      them if infections occur. If needed, patients will receive blood transfusions for their MDS.
      Side effects of alemtuzumab involve a temporarily significant lowering of the number of red
      blood cells, white cells, and platelets. Side effects of the infusion can be rigidity, or
      stiffness, and fever, as well as risks of infections resulting from the decrease of white
      blood cells. Blood counts and reactions to all procedures will be carefully monitored
      throughout the study. After patients receive the last dose of alemtuzumab, they will have
      follow-up by their referring doctor or at NIH. They must be able to return to NIH after 1
      month, 3 months, 6 months, and annually for 5 years after the study. At follow-up visits,
      there will be blood tests to reevaluate blood counts and test for the presence of viruses.
      Blood tests will be done weekly for the first 3 months after patients have completed taking
      alemtuzumab, every other week until 6 months, and then annually for 5 years. There will also
      be a repeat ECHO at the 3-month visit, and a repeat bone marrow biopsy at the 5-month and
      12-month follow-up visits, and as needed after that.

      This study may or may not have a direct benefit for participants. For some, the antibody may
      improve blood counts and decrease the need for transfusions. Knowledge gained in the study
      may help people in the future.
    

Detailed description: 
      Many bone marrow failure syndromes in humans are now recognized to result from immunological
      mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of
      myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia,
      leukopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a
      wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CsA)
      and horse antithymocyte globulin (h-ATG). However, non-response and relapse continues to be a
      problem. Why some patients do not respond initially or others respond and then relapse is
      unclear. Autoreactive T cells may be resistant to the effect of h-ATG/CsA (non-responders),
      while in others, residual autoreactive T cells expand post-treatment leading to hematopoietic
      stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel, less toxic
      immunosuppressive regimens that increase response rates and hematologic recovery and decrease
      relapse rates are needed.

      One such novel therapy, alemtuzumab (Campath[R]) is a humanized IgG1 monoclonal antibody
      directed against the CD52 protein, which is highly expressed on all lymphoid cells and
      monocytes. Alemtuzumab (Campath[R]), produces profound and persistent lymphopenia, affecting
      predominantly the CD4+ T cell subset. This property has made it attractive in the treatment
      of a wide range of diseases including rheumatoid arthritis, multiple sclerosis, ocular
      inflammatory disease, lymphoid malignancies, organ allograft rejection, and in conditioning
      regimens in stem cell transplantation to prevent graft failure and graft-versus-host disease.

      We therefore propose a non-randomized, off label, pilot, Phase I/II study of alemtuzumab
      (Campath) in MDS patients who are likely to respond to immunosuppression.

      Primary endpoints will be changes in peripheral blood counts (platelets, absolute neutrophil
      count, reticulocyte count, hemoglobin). Secondary endpoints (in transfusion-dependent
      patients) include improvement in the transfusion requirements (measured as decrease in the
      number of transfusion administered on as needed basis), duration of response, late effects of
      treatment, relapse and survival.
    

Intervention name(s): Alemtuzumab (Campath)
Intervention type(s): Drug
Intervention MeSH terms: Alemtuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Immunosuppression; T Cells; Hematopoiesis; Anti-CD52; Monoclonal Antibody Therapy