A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome
Condition: Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Alemtuzumab (Campath)
Intervention MeSH terms: Alemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 72 Years
Healthy volunteers: No
Keywords: Immunosuppression; T Cells; Hematopoiesis; Anti-CD52; Monoclonal Antibody Therapy

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. MDS with WHO classification of RA, RARS, RCMD-RS, RCUD, and RCMD and RAEB-1 (all
                  subtypes of MDS with the exception of RAEB 2, CMML, and MDS/MPN overlap)

               2. Anemia requiring transfusion support with at least one unit of packed red blood
                  cells per month for greater than or equal to 2 months

                  OR

                  Anemia (hemoglobin less than 9 or a reticulocyte count less than 60,000)

                  OR

                  thrombocytopenia (platelet count less than 50000/ul)

                  OR

                  neutropenia (absolute neutrophil count less than 500/ul).

               3. Off all other treatments for MDS (except filgrastim (G-CSF), erythropoietin, and
                  transfusion support and related medications) for at least four weeks. Filgrastim
                  (G-CSF) can be used before, during and after the protocol treatment for patients
                  with documented neutropenia (less than 500/Ul) as long as they meet the criteria
                  for anemia and/or thrombocytopenia as stated above.

               4. Ages 18-72 (inclusive)

        EXCLUSION CRITERIA:

          1. Chronic myelomonocytic leukemia (CMML), MDS/MPN overlap, WHO RAEB-2

          2. Secondary MDS

          3. Failure to respond to prior therapy with ATG or ATG/CsA

          4. Prior therapy with combination chemotherapy

          5. Transformation to acute leukemia (FAB sub-group RAEB-T, i.e., greater than 20% blasts
             in marrow aspirate)

          6. Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old
             Man's Beard) within 2 weeks of enrollment.

          7. Active infection not adequately responding to appropriate therapy

          8. HIV positive patients

          9. Active malignant disease (excluding non-melanoma skin carcinoma)

         10. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,
             infectious, or metabolic disease of such severity that it would preclude the patient's
             ability to tolerate protocol therapy or that death within 7-10 days is likely.

         11. Life expectancy less than 6 months

         12. Low predicted probability of response

         13. Previous hypersensitivity to alemtuzumab (Campath[R]) or its components

         14. Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy
             if of childbearing potential

         15. Not able to understand the investigational nature of the study or give informed
             consent