A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (MDS)
18 Years
72 Years
Both
Myelodysplastic Syndromes
Trial Information
A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (MDS)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Hematologic response (complete or partial) at 3 months after the first dose of alemtuzumab and sustained on greater than or equal to 2 serial measurements performed 1 month apart.
Safety Issue:
No
Principal Investigator
Ronan G Desmond, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Heart, Lung, and Blood Institute (NHLBI)
Authority:
United States: Federal Government
Study ID:
050206
NCT ID:
NCT00217594
Start Date:
July 2005
Completion Date:
June 2015
Related Keywords:
- Myelodysplastic Syndromes
- Immunosuppression
- T Cells
- Hematopoiesis
- Anti-CD52
- Monoclonal Antibody Therapy
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
