Protocol Number: 05-H-0206

Title:

A Pilot Study of Alemtuzumab (Campath[R]) in Patients with Myelodysplastic Syndrome (MDS)

Number:

05-H-0206

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.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1) MDS with WHO classification of RA, RARS, RCMD-RS, and RCMD and RAEB-1

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

5) High or intermediate predicted probability of response.

Patients age in years plus duration of RCTD in months

Greater than 58 DR15 negative patients and greater than 72 DR15 positive patients with a Low Predicted Probability of Response

50-58 DR15 negative patients with 64-72 DR15 positive patients with an Intermediate Predicted Probability of Response

Less than 50 DR15 negative patients and less than 64 DR15 positive patients with a High Predicted Probability of Response

EXCLUSION CRITERIA:

1) Chronic myelomonocytic leukemia (CMML), 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

Special Instructions:

Currently Not Provided

Keywords:

Immunosuppression

T Cells

Hematopoiesis

Anti-CD52

Monoclonal Antibody Therapy

Recruitment Keyword(s):

None

Condition(s):

Myelodysplastic Syndromes

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Alemtuzumab (Campath)

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Nydegger UE. Suppressive and substitutive immunotherapy: an essay with a review of recent literature. Immunol Lett. 1985;9(4):185-90. Review. No abstract available.

Tichelli A, Gratwohl A, Wuersch A, Nissen C, Speck B. Antilymphocyte globulin for myelodysplastic syndrome. Br J Haematol. 1988 Jan;68(1):139-40. No abstract available.

Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer. 1997 Apr 15;79(8):1548-51.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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