A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome
Status: | Completed |
---|---|
Conditions: | Blood Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - 72 |
Updated: | 11/1/2018 |
Start Date: | July 21, 2005 |
End Date: | February 6, 2017 |
A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (MDS)
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.
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.
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.
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:
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
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials